ArticleCell metabolism2021
FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption.
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Article in Cell metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 238 papers, 2 of them syntheses that pooled it.
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238citing papers in PubMed, 2 pooled it
39.0field-weighted citation impact, top 1% of its field
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Who cites it
238 citing papers in PubMed, 2 syntheses or guidelines pooled it, 427 citations in OpenAlex.
- Pharmacological Mechanisms of Bile Acids Targeting the Farnesoid X Receptor.International journal of molecular sciences · 2024Pooled it
- Alterations in Circulating Bile Acids in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis.Biomolecules · 2023Pooled it
- Tamoxifen induced hepatotoxicity via gut microbiota-mediated hyodeoxycholic acid depletion and Farnesoid X receptor signaling disruption.Gut microbes · 2026Article
- A novel exopolysaccharide fromGut microbes · 2026Article
- A systematic transcriptomic atlas and predictive framework for metabolite-driven T cell state transitions.iScience · 2026Article
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- The Bile Acid Signaling Axis: Deciphering the Roles of FXR and TGR5 in Hepatic Steatosis, Fibrosis, and Cancer.Pharmacology research & perspectives · 2026Review
- Mild alkaline phosphatase elevation associates with increased mortality and major adverse liver outcomes in MASLD.Hepatology communications · 2026Article
- mTORC1-TFEB/TFE3 signaling is associated with bile acid diversification during hepatic metabolic adaptation.Science advances · 2026Article
- Expanding bile acid diversityNatural product reports · 2026Review
- Mechanism of FXR signaling: from liver inflammation to hepatocellular carcinoma.Biochemistry and biophysics reports · 2026Review
- Taurolithocholic acid alleviates hepatic glycolipid dysregulation in low-birth-weight piglets by activating HNF4α and FXR.Journal of animal science and biotechnology · 2026Article
- Intestinal lipase inhibition uncouples diet-induced obesity from MASH by remodeling the hepatic lipidome in mice.Journal of lipid research · 2026Article
- CEBPG-Mediated Palmitic Acid Adaptation of Cancer-Associated Fibroblasts Drives Metastasis of Oral Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Hepatic FXR deficiency exacerbates dyslipidemia by disrupting the gut-liver axis via bile acid disorder and gut microbiota dysbiosis.Journal of translational medicine · 2026Article
- Bile acids as a predictor for all-cause mortality in peritoneal dialysis patients: a retrospective cohort study.BMC nephrology · 2026Article
- Targeting the Gut-Heart Axis in Atherosclerosis: Microbial Metabolites, Molecular Mechanisms, and Precision Therapeutics.Probiotics and antimicrobial proteins · 2026Review
- Liver fibrosis in metabolic dysfunction-associated steatotic liver disease: epidemiology, risk stratification and therapeutics.BMJ open gastroenterology · 2026Review
- Gut microbiota dysbiosis induced by tibial dyschondroplasia in turn accelerates disease pathogenesis through the gut-bone axis in broilers.Poultry science · 2026Article
178 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 4 institutions in 3 countries.
Bethan L CliffordDepartment of Medicine, Division of Cardiology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Leslie R SedgemanDepartment of Medicine, Division of Cardiology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Kevin J WilliamsDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Lipidomics Core Facility, Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Pauline MorandDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Angela ChengDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Kelsey E JarrettDepartment of Medicine, Division of Cardiology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Alvin P ChanDepartment of Medicine, Division of Cardiology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Madelaine C Brearley-SholtoDepartment of Medicine, Division of Cardiology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Annika WahlströmDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Julianne W AshbyDepartment of Medicine, Division of Cardiology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
William BarshopDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
James WohlschlegelDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Anna C CalkinLipid Metabolism & Cardiometabolic Disease Laboratory, Baker Heart & Diabetes Institute, Melbourne, VIC, Australia; Central Clinical School, Monash University, Melbourne, VIC, Australia.
Yingying LiuLipid Metabolism & Cardiometabolic Disease Laboratory, Baker Heart & Diabetes Institute, Melbourne, VIC, Australia; Molecular Metabolism & Ageing Laboratory, Baker Heart & Diabetes Institute, Melbourne, VIC, Australia.
Anders ThorellKarolinska Institutet, Department of Clinical Science, Danderyd Hospital and Department of Surgery, Ersta Hospital, Stockholm, Sweden.
Peter J MeikleMetabolomics Laboratory, Baker Heart & Diabetes Institute, Melbourne, VIC, Australia.
Brian G DrewCentral Clinical School, Monash University, Melbourne, VIC, Australia; Molecular Metabolism & Ageing Laboratory, Baker Heart & Diabetes Institute, Melbourne, VIC, Australia.
Julia J MackDepartment of Medicine, Division of Cardiology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Hanns-Ulrich MarschallDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Elizabeth J TarlingDepartment of Medicine, Division of Cardiology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center (JCCC), UCLA, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Peter A EdwardsDepartment of Medicine, Division of Cardiology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Thomas Q de Aguiar VallimDepartment of Medicine, Division of Cardiology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center (JCCC), UCLA, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA. Electronic address: tvallim@mednet.ucla.edu.
University of California, Los Angeles · USBaker Heart and Diabetes Institute · AUUniversity of Gothenburg · SEKarolinska Institutet · SE
Funding
UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7MGASTROENTEROLOGYT32DK007180 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JENSEN, DENNIS MICHAEL · 1986 to 2025
$10.0MVascular Biology Training GrantT32HL069766 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2002 to 2022
$7.4MSystems Genetics Dissection of Non-alcoholic SteatohepatitisR01DK117850 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Aldons Jake Lusis · 2019 to 2026
$4.6MProteolytic Control of Iron Metabolism by the Ubiquitin Ligase FBXL5R01GM089778 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WOHLSCHLEGEL, JAMES AKIRA · 2010 to 2023
$4.0MATP Binding Cassette Transporters in Health and DiseaseR01DK128952 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TARLING, ELIZABETH JOANNA, VALLIM, THOMAS A · 2021 to 2024
$2.4MNovel FXR-dependent Molecular Mechanisms in the Regulation of Liver MetabolismR01DK118064 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EDWARDS, PETER A, VALLIM, THOMAS A · 2019 to 2022
$2.1MCaltech/UCLA Individualized Theranostic Engineering to Advance Metabolic System (iTEAM)T32EB027629 · NIBIB · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Dino Di Carlo, Azita Emami · 2020 to 2026
$2.0MPost-Translational Regulation of Lipid MetabolismR01HL136543 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TARLING, ELIZABETH JOANNA · 2017 to 2021
$1.9MTranscriptional control of microRNAs in lipid metabolism and atherosclerosisR01HL122677 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VALLIM, THOMAS A · 2016 to 2020
$1.9MNovel Post-Transcriptional Regulators of Lipid MetabolismR01DK112119 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VALLIM, THOMAS A · 2017 to 2020
$1.7MNovel transcriptional regulators of bile acid metabolism and hepatotoxicityR01DK102559 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EDWARDS, PETER A · 2014 to 2017
$1.3MNHLBI NIH HHS K99 HL118161NHLBI NIH HHS R00 HL118161NHLBI NIH HHS R01 HL122677NHLBI NIH HHS R01 HL136543NHLBI NIH HHS T32 HL069766NIBIB NIH HHS T32 EB027629NIDDK NIH HHS K08 DK146180NIDDK NIH HHS R01 DK102559NIDDK NIH HHS R01 DK112119NIDDK NIH HHS R01 DK117850NIDDK NIH HHS R01 DK118064NIDDK NIH HHS R01 DK128952NIDDK NIH HHS T32 DK007180NIGMS NIH HHS R01 GM089778NIGMS NIH HHS T32 GM007185
Abstract
FXR agonists are used to treat non-alcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids. Here, we show that FXR activation with the FXR agonist GSK2324 controls hepatic lipids via reduced absorption and selective decreases in fatty acid synthesis. Using comprehensive lipidomic analyses, we show that FXR activation in mice or humans specifically reduces hepatic levels of mono- and polyunsaturated fatty acids (MUFA and PUFA). Decreases in MUFA are due to FXR-dependent repression of Scd1, Dgat2, and Lpin1 expression, which is independent of SHP and SREBP1c. FXR-dependent decreases in PUFAs are mediated by decreases in lipid absorption. Replenishing bile acids in the diet prevented decreased lipid absorption in GSK2324-treated mice, suggesting that FXR reduces absorption via decreased bile acids. We used tissue-specific FXR KO mice to show that hepatic FXR controls lipogenic genes, whereas intestinal FXR controls lipid absorption. Together, our studies establish two distinct pathways by which FXR regulates hepatic lipids.
Indexed as
Bile Acids and SaltsNon-alcoholic Fatty Liver DiseaseAnimalsBileHumansLipidsLiverMiceMice, Inbred C57BLPhosphatidate PhosphataseReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearBile Acids and SaltsLipidsLpin1 protein, mousePhosphatidate PhosphataseReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and Nuclearbile acidsFXRintestinal lipid absorptionNAFLD
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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.