ArticleNature metabolism2024
Inhibition of hepatic oxalate overproduction ameliorates metabolic dysfunction-associated steatohepatitis.
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Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20citing papers in PubMed
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Who cites it
20 citing papers in PubMed.
- Liver-specific phenotypic aging, behavior and genetic risks, and long-term liver-related outcomes.GeroScience · 2026Article
- Article
- Whole genome copy number variation analysis to detect genomic regions for resistance to Haemonchus contortus in Sheep.BMC genomics · 2026Article
- Metabolic Pathways Linking Atherosclerotic Cardiovascular Disease With Metabolic Dysfunction-Associated Steatotic Liver Disease.Current atherosclerosis reports · 2026Review
- Obesity, Metabolic Syndrome, Diabetes and Kidney Stones: Strengthening Links Over Time?TouchREVIEWS in endocrinology · 2026Review
- Circadian disruption exacerbates MASH by reducingiScience · 2026Article
- Sex-based multiomics analysis uncovers metabolic and molecular mediators linking MASH and atherosclerosis.JHEP reports : innovation in hepatology · 2026Article
- Targeting Oxalate Production by Combining Enzyme Inhibition and Proteolysis Activation: A Novel Therapeutic Approach for Primary Hyperoxaluria Type 1.Journal of medicinal chemistry · 2026Article
- Allyl isothiocyanate ameliorates metabolic dysfunction-associated steatotic liver diseaseWorld journal of gastroenterology · 2026Article
- Lactate attenuates hepatic ischemia-reperfusion injury by reducing intrahepatic inflammation and suppressing hepatocyte-neutrophil interaction via the IL-33/ST2 pathway.Cell communication and signaling : CCS · 2026Article
- Integrated Bioinformatics Analysis Revealing that the NSDHL Gene Might Be Associated with the Progression of Western HFD/SW-Induced Hepatocellular CarcinomaEndocrine, metabolic & immune disorders drug targets · 2026Article
- Bioinformatics analysis reveals the association of bile acid metabolism-related genes with sepsis.PloS one · 2026Article
- LNP-mediated in vivo base editing corrects Agxt to cure primary hyperoxaluria type 1.Clinical and translational medicine · 2025Article
- Factors Influencing Oxalate Synthesis in Healthy Volunteers.Journal of endourology · 2025Article
- Resolvin D1-mediated cellular crosstalk protects against MASH.JHEP reports : innovation in hepatology · 2025Article
- Colonization withbioRxiv : the preprint server for biology · 2025Article
- EHBP1 suppresses liver fibrosis in metabolic dysfunction-associated steatohepatitis.Cell metabolism · 2025Article
- Metabolic dysfunction associated steatotic liver and kidney stones: what is going on?Current opinion in nephrology and hypertension · 2025Review
- Rutin ameliorates calcium oxalate crystal-induced kidney injury through anti-oxidative stress and modulation of intestinal flora.Urolithiasis · 2025Article
- Harnessing glycolysis in gastric cancer: molecular targets, therapeutic strategies, and clinical horizons.Frontiers in immunology · 2025Review
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Authors and funding
45 authors.
Sandeep DasDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.ORCID http://orcid.org/0000-0002-6722-3909
Alexandra C FinneyDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.ORCID http://orcid.org/0000-0003-1575-4975
Sumit Kumar AnandDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.ORCID http://orcid.org/0000-0003-3719-0744
Sumati RohillaDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
Yuhao LiuDepartment of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, USA.
Nilesh PandeyDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
Alia GhrayebDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.ORCID http://orcid.org/0000-0002-2583-0874
Dhananjay KumarDepartment of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
Kelley NunezInstitute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA, USA.ORCID http://orcid.org/0000-0002-0004-317X
Zhipeng LiuDepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN, USA.
Fabio AriasDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.ORCID http://orcid.org/0000-0002-9906-6450
Ying ZhaoDepartment of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, USA.
Brenna H Pearson-GallionDepartment of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.ORCID http://orcid.org/0000-0001-9335-119X
M Peyton McKinneyDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.ORCID http://orcid.org/0009-0005-4105-6304
Koral S E RichardDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
Jose A Gomez-VidalDepartamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Granada, Spain.ORCID http://orcid.org/0000-0003-0937-698X
Chowdhury S AbdullahDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.ORCID http://orcid.org/0000-0001-5771-220X
Elizabeth D CockerhamDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.ORCID http://orcid.org/0000-0002-8549-1229
Joseph EniafeDepartment of Microbiology and Immunology, Center of Applied Immunology and Pathological Processes, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
Andrew D YurochkoDepartment of Microbiology and Immunology, Center of Applied Immunology and Pathological Processes, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.ORCID http://orcid.org/0000-0002-6452-5813
Tarek MagdyDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
Christopher B PattilloDepartment of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
Christopher G KevilDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.ORCID http://orcid.org/0000-0003-0863-7260
Babak RazaniDivision of Cardiology and Vascular Medicine Institute, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-7172-9240
Md Shenuarin BhuiyanDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
Erin H SeeleyDepartment of Chemistry, University of Texas at Austin, Austin, TX, USA.ORCID http://orcid.org/0000-0002-8000-5754
Gretchen E GallianoDepartment of Pathology, Ochsner Clinic Foundation, New Orleans, LA, USA.ORCID http://orcid.org/0000-0002-4120-4566
Bo WeiMetabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-5573-5715
Lin TanMetabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Iqbal MahmudMetabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7729-8122
Ida SurakkaDepartment of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-6669-5541
Minerva T Garcia-BarrioDepartment of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-3381-3847
Philip L LorenziMetabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-0385-7774
Eyal GottliebDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-9770-0956
Eduardo SalidoDepartment of Pathology, Hospital Universitario de Canarias, Universidad de La Laguna, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Tenerife, Spain.ORCID http://orcid.org/0000-0001-9599-9854
Jifeng ZhangDepartment of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-5161-4705
A Wayne OrrDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.ORCID http://orcid.org/0000-0002-2377-213X
Wanqing LiuDepartment of Pharmaceutical Sciences and Department of Pharmacology, Wayne State University, Detroit, MI, USA.
Monica Diaz-GavilanDepartamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Granada, Spain.ORCID http://orcid.org/0000-0002-7868-7231
Y Eugene ChenDepartment of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, MI, USA.
Nirav DhaneshaDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
Paul T ThevenotInstitute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA, USA.ORCID http://orcid.org/0000-0002-6483-6259
Ari J CohenInstitute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA, USA.ORCID http://orcid.org/0000-0003-1224-8647
Arif YurdagulDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.ORCID http://orcid.org/0000-0002-7613-6313
Oren RomDepartment of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA. oren.rom@lsuhs.edu.ORCID http://orcid.org/0000-0002-9272-086X
Funding
The Administrative CoreP01AI127335 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI Felicia D Goodrum · 2017 to 2026
$24.6MRegional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3MProject 4-Tracking cytomegalovirus-primed long-lived NK cells in salivary glandP20GM134974 · NIGMS · LOUISIANA STATE UNIV HSC SHREVEPORT · PI ANDREW D YUROCHKO · 2021 to 2026
$15.0MUsing genetics to discover mechanisms of myocardial infarctionR01HL109946 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI YUQING Eugene CHEN, Ida Liisa Surakka · 2011 to 2026
$8.9MKLF14 and Cardiovascular DiseaseR01HL134569 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE · 2017 to 2024
$5.3MAnalysis of HCMV Infection of Monocytes and MacrophagesR01AI056077 · NIAID · LOUISIANA STATE UNIV HSC SHREVEPORT · PI YUROCHKO, ANDREW D · 2004 to 2020
$4.7MTHE ROLE OF MACROPHAGE LYSOSOMAL BIOGENESIS IN ATHEROSCLEROSISR01HL125838 · NHLBI · WASHINGTON UNIVERSITY · PI RAZANI, BABAK · 2015 to 2025
$4.6MNck Adaptor Proteins in Atherogenic Endothelial ActivationR01HL133497 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI ORR, ANTHONY WAYNE · 2016 to 2024
$3.8MDissecting the Impact of Dietary Protein on Macrophage mTOR Signaling and AtherosclerosisR01HL159461 · NHLBI · WASHINGTON UNIVERSITY · PI Bettina Mittendorfer, Babak Razani · 2022 to 2026
$3.3MNitro-Fatty Acids and Cardiovascular DiseaseR01HL162294 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE, GARCIA-BARRIO, MINERVA T · 2022 to 2025
$2.9MBAF60c and abdominal aortic aneurysmR01HL153710 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZHANG, JIFENG · 2021 to 2025
$2.7MSigmar1 in lipid metabolismR01HL145753 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI BHUIYAN, MD. SHENUARIN · 2019 to 2023
$2.6MAmerican Heart Association (American Heart Association, Inc.) 19POST34380224American Heart Association (American Heart Association, Inc.) 20CDA3560123American Heart Association (American Heart Association, Inc.) 23POST1026505American Heart Association (American Heart Association, Inc.) 24POST1196650American Heart Association (American Heart Association, Inc.) 24POST1199805BLRD VA I01 BX003415Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) RP190617NHLBI NIH HHS K99 HL145131NHLBI NIH HHS K99 HL150233NHLBI NIH HHS R00 HL145131NHLBI NIH HHS R00 HL150233NHLBI NIH HHS R01 HL109946NHLBI NIH HHS R01 HL125838NHLBI NIH HHS R01 HL133497NHLBI NIH HHS R01 HL134569NHLBI NIH HHS R01 HL138139NHLBI NIH HHS R01 HL139755NHLBI NIH HHS R01 HL141155NHLBI NIH HHS R01 HL145753NHLBI NIH HHS R01 HL153710NHLBI NIH HHS R01 HL158546NHLBI NIH HHS R01 HL159461NHLBI NIH HHS R01 HL159871NHLBI NIH HHS R01 HL162294NHLBI NIH HHS R01 HL167758NHLBI NIH HHS R01 HL172970NHLBI NIH HHS R01 HL173972NHLBI NIH HHS T32 HL155022NIAID NIH HHS P01 AI127335NIAID NIH HHS R01 AI056077NIAID NIH HHS R56 AI159672NIDDK NIH HHS F31 DK131859NIDDK NIH HHS P30 DK020572NIDDK NIH HHS R01 DK134011NIDDK NIH HHS R01 DK136685NIGMS NIH HHS P20 GM134974U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL109946U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL133497U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL134569U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL138139U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL139755U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL141155U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL145131U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL145753U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL145753-01S1U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL145753-03S1U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL150233U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL153710U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL158546U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL159871U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL162294U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL167758U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI127335U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R56-AI159672U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK131859U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK134011U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK136685U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) P20GM134974
Abstract
The incidence of metabolic dysfunction-associated steatohepatitis (MASH) is on the rise, and with limited pharmacological therapy available, identification of new metabolic targets is urgently needed. Oxalate is a terminal metabolite produced from glyoxylate by hepatic lactate dehydrogenase (LDHA). The liver-specific alanine-glyoxylate aminotransferase (AGXT) detoxifies glyoxylate, preventing oxalate accumulation. Here we show that AGXT is suppressed and LDHA is activated in livers from patients and mice with MASH, leading to oxalate overproduction. In turn, oxalate promotes steatosis in hepatocytes by inhibiting peroxisome proliferator-activated receptor-α (PPARα) transcription and fatty acid β-oxidation and induces monocyte chemotaxis via C-C motif chemokine ligand 2. In male mice with diet-induced MASH, targeting oxalate overproduction through hepatocyte-specific AGXT overexpression or pharmacological inhibition of LDHA potently lowers steatohepatitis and fibrosis by inducing PPARα-driven fatty acid β-oxidation and suppressing monocyte chemotaxis, nuclear factor-κB and transforming growth factor-β targets. These findings highlight hepatic oxalate overproduction as a target for the treatment of MASH.
Indexed as
Fatty LiverLiverOxalatesAnimalsHepatocytesHumansMaleMiceMice, Inbred C57BLPPAR alphaTransaminasesAlanine-glyoxylate transaminaseOxalatesPPAR alphaTransaminases
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