{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:08:53Z","timestamp":1785431333374,"version":"3.56.0"},"reference-count":130,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AA030289"],"award-info":[{"award-number":["R01AA030289"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R01AA030289"],"award-info":[{"award-number":["R01AA030289"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Peroxisomes are essential metabolic organelles that support core aspects of cellular homeostasis. In the hepatocytes, peroxisomes govern key aspects of cellular homeostasis, including processing lipid substrates that are inadequately handled by mitochondria, controlling hydrogen peroxide metabolism, and regulating bile acid synthesis. Increasing evidence indicates that these organelles are not merely auxiliary metabolic compartments but active contributors to the development and progression of liver disease. Dynamic alterations in peroxisomal proteins and function are being noted. Across metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cholestatic disorders, fibrosis, and hepatocellular carcinoma, peroxisomes undergo remodeling that shows a change from adaptive reactions to maladaptive states. These changes perturb signaling pathways that regulate inflammation, stress responses, and cell fate. In addition, because peroxisomes operate within an interconnected organelle network, their dysfunction propagates to mitochondria, endoplasmic reticulum, and other cellular systems, amplifying metabolic and cellular stress. This review summarizes current understanding of how peroxisomal pathways contribute to liver disease, highlighting mechanisms involving lipid accumulation, oxidative stress, and disrupted organelle crosstalk. How peroxisome-dependent control of circulating metabolites links hepatic injury to extrahepatic organ systems is further discussed. At the end, emerging therapeutic strategies for liver disease targeting peroxisomal pathways are discussed. Together, the emerging understanding of peroxisomal remodeling, metabolic regulation, organelle crosstalk, and inter-organ communication positions peroxisomes as active and dynamic regulators of liver disease and potential targets for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/biom16060895","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:49:42Z","timestamp":1781743782000},"page":"895","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peroxisomes in Liver Diseases: From Metabolite Quality Control to Inter-Organelle and Inter-Organ Signaling"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9635-8063","authenticated-orcid":false,"given":"Carolina","family":"Hogerty","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA"},{"name":"The Liver Center, University of Kansas Medical Center, Kansas City, KS 66160, USA"},{"name":"Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0722-195X","authenticated-orcid":false,"given":"Yantao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA"},{"name":"The Liver Center, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5486-4427","authenticated-orcid":false,"given":"Weiran","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA"},{"name":"The Liver Center, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Weinman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA"},{"name":"The Liver Center, University of Kansas Medical Center, Kansas City, KS 66160, USA"},{"name":"Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6608-2537","authenticated-orcid":false,"given":"Wei","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA"},{"name":"The Liver Center, University of Kansas Medical Center, Kansas City, KS 66160, USA"},{"name":"Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s00418-024-02349-y","article-title":"Seventy years of peroxisome research: Current advances and future perspectives","volume":"163","author":"Carmichael","year":"2025","journal-title":"Histochem. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev.biochem.74.082803.133329","article-title":"Biochemistry of mammalian peroxisomes revisited","volume":"75","author":"Wanders","year":"2006","journal-title":"Annu. Rev. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ceb.2016.02.017","article-title":"The peroxisome as a cell signaling organelle","volume":"39","author":"Tripathi","year":"2016","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Carmichael, R.E. (2025). Peroxisome dynamics and inter-organelle interactions in neuronal health and disease. Front. Mol. Neurosci., 18.","DOI":"10.3389\/fnmol.2025.1603632"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/jimd.12083","article-title":"Organelle interplay\u2014Peroxisome interactions in health and disease","volume":"43","author":"Schrader","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bose, M., Yergeau, C., D\u2019Souza, Y., Cuthbertson, D.D., Lopez, M.J., Smolen, A.K., and Braverman, N.E. (2022). Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review. Cells, 11.","DOI":"10.3390\/cells11121891"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s00418-018-1722-5","article-title":"The peroxisome: An update on mysteries 2.0","volume":"150","author":"Islinger","year":"2018","journal-title":"Histochem. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00418-023-02259-5","article-title":"The peroxisome: An update on mysteries 3.0","volume":"161","author":"Kumar","year":"2024","journal-title":"Histochem. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.cmet.2014.01.002","article-title":"Peroxisomes: A nexus for lipid metabolism and cellular signaling","volume":"19","author":"Lodhi","year":"2014","journal-title":"Cell Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e100218","DOI":"10.1136\/egastro-2025-100218","article-title":"Steatotic liver disease and cancer: From pathogenesis to therapeutic targets","volume":"3","author":"Yang","year":"2025","journal-title":"eGastroenterology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.bbamcr.2015.09.035","article-title":"Hepatic dysfunction in peroxisomal disorders","volume":"1863","author":"Baes","year":"2016","journal-title":"Biochim. Biophys. Acta BBA-Mol. Cell Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Vinoy, N., Huang, G., Wallace, D.F., and Subramaniam, V.N. (2025). Peroxisome Dysfunction and Steatotic Liver Disease. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26178303"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ymgme.2008.11.165","article-title":"Toxicity of peroxisomal C27-bile acid intermediates","volume":"96","author":"Ferdinandusse","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101577","DOI":"10.1016\/j.molmet.2022.101577","article-title":"Peroxisomal regulation of energy homeostasis: Effect on obesity and related metabolic disorders","volume":"65","author":"Kleiboeker","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"ar156","DOI":"10.1091\/mbc.E24-06-0252","article-title":"Distinct peroxisome populations differentially respond to alcohol-associated hepatic injury","volume":"35","author":"Mitra","year":"2024","journal-title":"Mol. Biol. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1002\/hep.21532","article-title":"Bile acid treatment alters hepatic disease and bile acid transport in peroxisome-deficient PEX2 Zellweger mice","volume":"45","author":"Keane","year":"2007","journal-title":"Hepatology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1097\/HEP.0000000000000182","article-title":"Hepatic fibrosis: Targeting peroxisome proliferator-activated receptor alpha from mechanism to medicines","volume":"78","author":"Gong","year":"2023","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kim, J.A. (2020). Peroxisome Metabolism in Cancer. Cells, 9.","DOI":"10.3390\/cells9071692"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101835","DOI":"10.1016\/j.clinre.2021.101835","article-title":"Peroxisome-related genes in hepatocellular carcinoma correlated with tumor metabolism and overall survival","volume":"46","author":"Liu","year":"2022","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_20","first-page":"140","article-title":"The peroxisomes of human hepatocytes","volume":"36","author":"Sternlieb","year":"1977","journal-title":"Lab. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"EMBR201846864","DOI":"10.15252\/embr.201846864","article-title":"Peroxisome biogenesis, membrane contact sites, and quality control","volume":"20","author":"Farre","year":"2019","journal-title":"EMBO Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fujiki, Y., Okumoto, K., Mukai, S., Honsho, M., and Tamura, S. (2014). Peroxisome biogenesis in mammalian cells. Front. Physiol., 5.","DOI":"10.3389\/fphys.2014.00307"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/ddrr.1113","article-title":"Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives","volume":"17","author":"Braverman","year":"2013","journal-title":"Dev. Disabil. Res. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1038\/s41467-025-57053-9","article-title":"Peroxisomal core structures segregate diverse metabolic pathways","volume":"16","author":"Backer","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"119330","DOI":"10.1016\/j.bbamcr.2022.119330","article-title":"Molecular insights into peroxisome homeostasis and peroxisome biogenesis disorders","volume":"1869","author":"Fujiki","year":"2022","journal-title":"Biochim. Biophys. Acta BBA-Mol. Cell Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/978-3-030-60204-8_5","article-title":"Fatty Acid Oxidation in Peroxisomes: Enzymology, Metabolic Crosstalk with Other Organelles and Peroxisomal Disorders","volume":"1299","author":"Wanders","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1194\/jlr.R900009-JLR200","article-title":"Bile acids: The role of peroxisomes","volume":"50","author":"Ferdinandusse","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.1194\/jlr.R800026-JLR200","article-title":"Fifty years of advances in bile acid synthesis and metabolism","volume":"50","author":"Russell","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41392-024-01811-6","article-title":"Bile acid metabolism and signaling in health and disease: Molecular mechanisms and therapeutic targets","volume":"9","author":"Fleishman","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.brainresbull.2023.01.011","article-title":"Regulation of plasmalogen biosynthesis in mammalian cells and tissues","volume":"194","author":"Honsho","year":"2023","journal-title":"Brain Res. Bull."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101207","DOI":"10.1016\/j.plipres.2022.101207","article-title":"Compartmentalized regulation of lipid signaling in oxidative stress and inflammation: Plasmalogens, oxidized lipids and ferroptosis as new paradigms of bioactive lipid research","volume":"89","author":"Astudillo","year":"2023","journal-title":"Prog. Lipid Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"28280","DOI":"10.1021\/acs.jafc.4c06929","article-title":"Plasmalogens Reversed Oxidative Stress and Inflammatory Response Exacerbated by Damage to Cell Membrane Properties in Acute Liver Injury","volume":"72","author":"Mei","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1152\/physrev.00033.2016","article-title":"Redox Regulation of Homeostasis and Proteostasis in Peroxisomes","volume":"98","author":"Walker","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1089\/ars.2018.7515","article-title":"Redox Signaling from and to Peroxisomes: Progress, Challenges, and Prospects","volume":"30","author":"Fransen","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1093\/plphys\/kiab060","article-title":"Peroxisomes as redox-signaling nodes in intracellular communication and stress responses","volume":"186","author":"Sandalio","year":"2021","journal-title":"Plant Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.bbamcr.2015.09.014","article-title":"De novo peroxisome biogenesis: Evolving concepts and conundrums","volume":"1863","author":"Agrawal","year":"2016","journal-title":"Biochim. Biophys. Acta BBA-Mol. Cell Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3945\/an.113.003798","article-title":"PPAR-alpha as a key nutritional and environmental sensor for metabolic adaptation","volume":"4","author":"Contreras","year":"2013","journal-title":"Adv. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1038\/s12276-020-00503-9","article-title":"Peroxisome quality control and dysregulated lipid metabolism in neurodegenerative diseases","volume":"52","author":"Jo","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e202511183","DOI":"10.1083\/jcb.202511183","article-title":"Pexophagy meets physiology","volume":"225","author":"Clague","year":"2026","journal-title":"J. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1038\/s41467-018-03957-8","article-title":"Systematic mapping of contact sites reveals tethers and a function for the peroxisome-mitochondria contact","volume":"9","author":"Shai","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Fransen, M., Lismont, C., and Walton, P. (2017). The Peroxisome-Mitochondria Connection: How and Why?. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18061126"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.aac.2025.11.002","article-title":"Peroxisome-mitochondria contact-mediated ROS transfer: A key line of defence under plant stress","volume":"5","author":"Song","year":"2026","journal-title":"Adv. Agrochem"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1126\/science.adn2804","article-title":"ROS transfer at peroxisome-mitochondria contact regulates mitochondrial redox","volume":"389","author":"DiGiovanni","year":"2025","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Agrawal, G., and Subramani, S. (2013). Emerging role of the endoplasmic reticulum in peroxisome biogenesis. Front. Physiol., 4.","DOI":"10.3389\/fphys.2013.00286"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1093\/molbev\/msj103","article-title":"The evolutionary origin of peroxisomes: An ER-peroxisome connection","volume":"23","author":"Schluter","year":"2006","journal-title":"Mol. Biol. Evol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Joshi, A.S., and Cohen, S. (2019). Lipid Droplet and Peroxisome Biogenesis: Do They Go Hand-in-Hand?. Front. Cell Dev. Biol., 7.","DOI":"10.3389\/fcell.2019.00092"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1038\/s41467-018-05277-3","article-title":"Lipid droplet and peroxisome biogenesis occur at the same ER subdomains","volume":"9","author":"Joshi","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101185","DOI":"10.1016\/j.jhepr.2024.101185","article-title":"Lipid metabolism in MASLD and MASH: From mechanism to the clinic","volume":"6","author":"Carli","year":"2024","journal-title":"JHEP Rep."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Syed-Abdul, M.M. (2023). Lipid Metabolism in Metabolic-Associated Steatotic Liver Disease (MASLD). Metabolites, 14.","DOI":"10.3390\/metabo14010012"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"829","DOI":"10.4093\/dmj.2021.0274","article-title":"Peroxisomal Fitness: A Potential Protective Mechanism of Fenofibrate against High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice","volume":"46","author":"Jiang","year":"2022","journal-title":"Diabetes Metab. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e93626","DOI":"10.1172\/jci.insight.93626","article-title":"Peroxisomal beta-oxidation regulates whole body metabolism, inflammatory vigor, and pathogenesis of nonalcoholic fatty liver disease","volume":"3","author":"Giles","year":"2018","journal-title":"JCI Insight"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3800","DOI":"10.1074\/jbc.M116.763532","article-title":"Specific Inhibition of Acyl-CoA Oxidase-1 by an Acetylenic Acid Improves Hepatic Lipid and Reactive Oxygen Species (ROS) Metabolism in Rats Fed a High Fat Diet","volume":"292","author":"Zeng","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4214","DOI":"10.1038\/s41467-024-48471-2","article-title":"Liver ACOX1 regulates levels of circulating lipids that promote metabolic health through adipose remodeling","volume":"15","author":"Lu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.jare.2025.09.008","article-title":"Loss of hepatic ME1 ameliorates MASLD by Suppressing peroxisomal \u03b2-Oxidation and Activating Lipophagy\/Lipolysis","volume":"84","author":"Zhang","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Yang, Y., Yuan, W., He, K., Lin, C., Du, S., Kou, Y., and Nie, B. (2024). Inhibition of ACOX1 enhances the therapeutic efficacy of obeticholic acid in treating non-alcoholic fatty liver disease and mitigates its lipotoxicity. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1366479"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Chen, X., Wang, L., Denning, K.L., Mazur, A., Xu, Y., Wang, K., Lawrence, L.M., Wang, X., and Lu, Y. (2024). Hepatocyte-Specific PEX16 Abrogation in Mice Leads to Hepatocyte Proliferation, Alteration of Hepatic Lipid Metabolism, and Resistance to High-Fat Diet (HFD)-Induced Hepatic Steatosis and Obesity. Biomedicines, 12.","DOI":"10.20944\/preprints202403.1009.v1"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"115623","DOI":"10.1016\/j.celrep.2025.115623","article-title":"Peroxisomes are critical for a unique metabolic demand and survival of alveolar macrophages","volume":"44","author":"Matsushita","year":"2025","journal-title":"Cell Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Pratama, A.M., Bommel, H., Wihadmadyatami, H., Tjahjono, Y., Ergun, S., Bachhuka, A., and Karnati, S. (2025). Peroxisomes, PPARs, and Their Role in Macrophages. Cells, 14.","DOI":"10.3390\/cells14242021"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1002\/hep.23337","article-title":"Kupffer cells promote hepatic steatosis via interleukin-1beta-dependent suppression of peroxisome proliferator-activated receptor alpha activity","volume":"51","author":"Stienstra","year":"2010","journal-title":"Hepatology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1056\/NEJMoa2036205","article-title":"A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH","volume":"385","author":"Francque","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.freeradbiomed.2007.11.004","article-title":"CYP2E1 and oxidative liver injury by alcohol","volume":"44","author":"Lu","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.bbamcr.2006.09.006","article-title":"Peroxisomes and oxidative stress","volume":"1763","author":"Schrader","year":"2006","journal-title":"Biochim. Biophys. Acta BBA-Mol. Cell Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S0022-5347(24)07212-4","article-title":"The role of hydrogen peroxide and catalase in hepatic microsomal ethanol oxidation","volume":"1","author":"Thurman","year":"1973","journal-title":"Drug Metab. Dispos."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/S0022-3565(24)37949-2","article-title":"Peroxisomes are involved in the swift increase in alcohol metabolism","volume":"288","author":"Bradford","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0014-5793(88)80243-6","article-title":"Hepatic ethanol metabolism is mediated predominantly by catalase-H2O2 in the fasted state","volume":"238","author":"Handler","year":"1988","journal-title":"FEBS Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1006\/abbi.1993.1269","article-title":"Evidence that catalase is a major pathway of ethanol oxidation in vivo: Dose-response studies in deer mice using methanol as a selective substrate","volume":"303","author":"Bradford","year":"1993","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.freeradbiomed.2021.04.018","article-title":"PPARalpha agonist WY-14,643 enhances ethanol metabolism in mice: Role of catalase","volume":"169","author":"Chen","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.freeradbiomed.2023.08.016","article-title":"Under peroxisome proliferation acyl-CoA oxidase coordinates with catalase to enhance ethanol metabolism","volume":"208","author":"Chen","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.freeradbiomed.2021.08.005","article-title":"Activation of PPARalpha-catalase pathway reverses alcoholic liver injury via upregulating NAD synthesis and accelerating alcohol clearance","volume":"174","author":"Yue","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/j.bbamcr.2006.09.001","article-title":"Peroxisomes and bile acid biosynthesis","volume":"1763","author":"Ferdinandusse","year":"2006","journal-title":"Biochim. Biophys. Acta BBA-Mol. Cell Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"11289","DOI":"10.1073\/pnas.1613228113","article-title":"ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment","volume":"113","author":"Vilarinho","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1002\/hep.32517","article-title":"Beneficial effect of ursodeoxycholic acid in patients with acyl-CoA oxidase 2 (ACOX2) deficiency-associated hypertransaminasemia","volume":"76","author":"Herraez","year":"2022","journal-title":"Hepatology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1093\/hmg\/ddu448","article-title":"A novel bile acid biosynthesis defect due to a deficiency of peroxisomal ABCD3","volume":"24","author":"Ferdinandusse","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1194\/jlr.R005959","article-title":"Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism","volume":"51","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13578-023-01035-1","article-title":"Bile acid-mediated signaling in cholestatic liver diseases","volume":"13","author":"Zeng","year":"2023","journal-title":"Cell Biosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"737","DOI":"10.21037\/atm-20-5110","article-title":"The role of bile acids in cholestatic liver injury","volume":"9","author":"Cai","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/j.bbadis.2017.09.019","article-title":"Nuclear receptor FXR, bile acids and liver damage: Introducing the progressive familial intrahepatic cholestasis with FXR mutations","volume":"1864","author":"Cariello","year":"2018","journal-title":"Biochim. Biophys. Acta BBA-Mol. Basis Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.ymgme.2015.12.009","article-title":"Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines","volume":"117","author":"Braverman","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"11392","DOI":"10.1074\/jbc.M310284200","article-title":"Peroxisome proliferator-activated receptor gamma induces a phenotypic switch from activated to quiescent hepatic stellate cells","volume":"279","author":"Hazra","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3370","DOI":"10.2174\/09298673113209990136","article-title":"Hepatic PPARs: Their role in liver physiology, fibrosis and treatment","volume":"20","author":"Zardi","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e0154","DOI":"10.1097\/HC9.0000000000000154","article-title":"Peroxisome proliferator-activated receptor gamma activation ameliorates liver fibrosis-differential action of transcription factor EB and autophagy on hepatocytes and stellate cells","volume":"7","author":"Yum","year":"2023","journal-title":"Hepatol. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"115165","DOI":"10.1016\/j.celrep.2024.115165","article-title":"The adiponectin-PPARgamma axis in hepatic stellate cells regulates liver fibrosis","volume":"44","author":"Zhao","year":"2025","journal-title":"Cell Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"E2048","DOI":"10.1073\/pnas.1415111112","article-title":"Compromised peroxisomes in idiopathic pulmonary fibrosis, a vicious cycle inducing a higher fibrotic response via TGF-beta signaling","volume":"112","author":"Oruqaj","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/BF00711439","article-title":"Secondary alterations of human hepatocellular peroxisomes","volume":"18","year":"1995","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3851","DOI":"10.1002\/1097-0142(19930615)71:12<3851::AID-CNCR2820711210>3.0.CO;2-L","article-title":"Alterations of hepatocellular peroxisomes in patients with cancer. Catalase cytochemistry and morphometry","volume":"71","author":"Pauwels","year":"1993","journal-title":"Cancer"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1007\/s004280050432","article-title":"Immunocytochemical investigation of catalase and peroxisomal lipid beta-oxidation enzymes in human hepatocellular tumors and liver cirrhosis","volume":"435","author":"Litwin","year":"1999","journal-title":"Virchows Arch."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"EMBR201745124","DOI":"10.15252\/embr.201745124","article-title":"SIRT5 inhibits peroxisomal ACOX1 to prevent oxidative damage and is downregulated in liver cancer","volume":"19","author":"Chen","year":"2018","journal-title":"EMBO Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.canlet.2018.02.021","article-title":"Disruption of peroxisome function leads to metabolic stress, mTOR inhibition, and lethality in liver cancer cells","volume":"421","author":"Cai","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.clnu.2023.12.005","article-title":"Peroxisome proliferator-activated receptors: A key link between lipid metabolism and cancer progression","volume":"43","author":"Li","year":"2024","journal-title":"Clin. Nutr."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s00204-017-2094-7","article-title":"The PPAR\u03b1-dependent rodent liver tumor response is not relevant to humans: Addressing misconceptions","volume":"92","author":"Corton","year":"2018","journal-title":"Arch. Toxicol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.tox.2007.09.030","article-title":"PPARalpha: Mechanism of species differences and hepatocarcinogenesis of peroxisome proliferators","volume":"246","author":"Gonzalez","year":"2008","journal-title":"Toxicology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3849","DOI":"10.1158\/0008-5472.CAN-04-0322","article-title":"Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha","volume":"64","author":"Cheung","year":"2004","journal-title":"Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"8330","DOI":"10.18632\/oncotarget.2212","article-title":"Peroxisome proliferator activated receptor alpha inhibits hepatocarcinogenesis through mediating NF-kappaB signaling pathway","volume":"5","author":"Zhang","year":"2014","journal-title":"Oncotarget"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1007\/s00705-014-2105-4","article-title":"Peroxisome-localized hepatitis Bx protein increases the invasion property of hepatocellular carcinoma cells","volume":"159","author":"Han","year":"2014","journal-title":"Arch. Virol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1136\/gutjnl-2021-326789","article-title":"Gut microbiome and health: Mechanistic insights","volume":"71","author":"Tilg","year":"2022","journal-title":"Gut"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/j.1365-2362.1987.tb01131.x","article-title":"Bile acids in peroxisomal disorders","volume":"17","author":"Parmentier","year":"1987","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1124\/pr.113.008201","article-title":"Bile acid signaling in metabolic disease and drug therapy","volume":"66","author":"Li","year":"2014","journal-title":"Pharmacol. Rev."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Mori, H., Svegliati Baroni, G., Marzioni, M., Di Nicola, F., Santori, P., Maroni, L., Abenavoli, L., and Scarpellini, E. (2022). Farnesoid X Receptor, Bile Acid Metabolism, and Gut Microbiota. Metabolites, 12.","DOI":"10.3390\/metabo12070647"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2232143","DOI":"10.1080\/19490976.2023.2232143","article-title":"Gut microbiota-related bile acid metabolism-FXR\/TGR5 axis impacts the response to anti-alpha4beta7-integrin therapy in humanized mice with colitis","volume":"15","author":"Han","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Shi, L., Jin, L., and Huang, W. (2023). Bile Acids, Intestinal Barrier Dysfunction, and Related Diseases. Cells, 12.","DOI":"10.3390\/cells12141888"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1111\/apt.14949","article-title":"Bile acid homeostasis and intestinal dysbiosis in alcoholic hepatitis","volume":"48","author":"Ciocan","year":"2018","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.apsb.2015.01.006","article-title":"The human gut sterolbiome: Bile acid-microbiome endocrine aspects and therapeutics","volume":"5","author":"Ridlon","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trsl.2020.06.006","article-title":"The selective PPAR-delta agonist seladelpar reduces ethanol-induced liver disease by restoring gut barrier function and bile acid homeostasis in mice","volume":"227","author":"Chu","year":"2021","journal-title":"Transl. Res."},{"key":"ref_104","first-page":"98","article-title":"Review on Kidney-Liver Crosstalk: Pathophysiology of Their Disorders","volume":"26","author":"Rad","year":"2024","journal-title":"Cell J."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4783","DOI":"10.7150\/ijbs.100394","article-title":"Mechanisms of hepatic and renal injury in lipid metabolism disorders in metabolic syndrome","volume":"20","author":"Rong","year":"2024","journal-title":"Int. J. Biol. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.kint.2023.12.009","article-title":"Chronic kidney disease in a murine model of non-alcoholic steatohepatitis (NASH)","volume":"105","author":"Li","year":"2024","journal-title":"Kidney Int."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/cld.170","article-title":"Renal failure and liver transplantation","volume":"2","author":"Boyer","year":"2013","journal-title":"Clin. Liver Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.bbamcr.2015.12.005","article-title":"Peroxisomes in brain development and function","volume":"1863","author":"Berger","year":"2016","journal-title":"Biochim. Biophys. Acta BBA-Mol. Cell Res."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Yeo, X.Y., Tan, L.Y., Chae, W.R., Lee, D.Y., Lee, Y.A., Wuestefeld, T., and Jung, S. (2023). Liver\u2019s influence on the brain through the action of bile acids. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1123967"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3233\/ADR-220071","article-title":"The Pathological Effects of Circulating Hydrophobic Bile Acids in Alzheimer\u2019s Disease","volume":"7","author":"Ehtezazi","year":"2023","journal-title":"J. Alzheimers Dis. Rep."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.livres.2021.07.002","article-title":"Bile acid receptors and signaling crosstalk in the liver, gut and brain","volume":"5","author":"Ferrell","year":"2021","journal-title":"Liver Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"G852","DOI":"10.1152\/ajpgi.00521.2005","article-title":"Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation","volume":"290","author":"Reddy","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1053\/jhep.2003.50307","article-title":"Central role of PPARalpha-dependent hepatic lipid turnover in dietary steatohepatitis in mice","volume":"38","author":"Ip","year":"2003","journal-title":"Hepatology"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1007\/s00011-010-0226-0","article-title":"Effectiveness of the PPARgamma agonist, GW570, in liver fibrosis","volume":"59","author":"Yang","year":"2010","journal-title":"Inflamm. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e250206","DOI":"10.57264\/cer-2025-0206","article-title":"Network meta-analysis: Relative clinical efficacy and safety of elafibranor versus seladelpar as second-line treatment for patients with primary biliary cholangitis","volume":"15","author":"Jones","year":"2026","journal-title":"J. Comp. Eff. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.jhep.2014.10.039","article-title":"Molecular mechanism of PPARalpha action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease","volume":"62","author":"Pawlak","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.molmet.2014.02.002","article-title":"Integrated physiology and systems biology of PPARalpha","volume":"3","author":"Kersten","year":"2014","journal-title":"Mol. Metab."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1056\/NEJMoa2312100","article-title":"A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis","volume":"390","author":"Hirschfield","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1056\/NEJMoa2306185","article-title":"Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis","volume":"390","author":"Kowdley","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1007\/s00018-018-2860-6","article-title":"Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease","volume":"75","author":"Ipsen","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1002\/hep.28991","article-title":"New therapeutic concepts in bile acid transport and signaling for management of cholestasis","volume":"65","author":"Trauner","year":"2017","journal-title":"Hepatology"},{"key":"ref_122","first-page":"276","article-title":"Nonalcoholic fatty liver disease: Relationship to insulin sensitivity and oxidative stress. Treatment approaches using vitamin E, magnesium, and betaine","volume":"7","author":"Patrick","year":"2002","journal-title":"Altern. Med. Rev."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Allameh, A., Niayesh-Mehr, R., Aliarab, A., Sebastiani, G., and Pantopoulos, K. (2023). Oxidative Stress in Liver Pathophysiology and Disease. Antioxidants, 12.","DOI":"10.3390\/antiox12091653"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1056\/NEJMoa0907929","article-title":"Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis","volume":"362","author":"Sanyal","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"180","DOI":"10.4254\/wjh.v15.i2.180","article-title":"Antioxidant and anti-inflammatory agents in chronic liver diseases: Molecular mechanisms and therapy","volume":"15","author":"Zhang","year":"2023","journal-title":"World J. Hepatol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"512721","DOI":"10.1155\/2012\/512721","article-title":"Pexophagy: The selective degradation of peroxisomes","volume":"2012","author":"Till","year":"2012","journal-title":"Int. J. Cell Biol."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Cheng, C.F., Ku, H.C., and Lin, H. (2018). PGC-1alpha as a Pivotal Factor in Lipid and Metabolic Regulation. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113447"},{"key":"ref_128","first-page":"55","article-title":"Pexophagy: Molecular Mechanisms and Implications for Health and Diseases","volume":"41","author":"Cho","year":"2018","journal-title":"Mol. Cells"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"20376","DOI":"10.1073\/pnas.1009176107","article-title":"Transcriptional coactivator PGC-1alpha promotes peroxisomal remodeling and biogenesis","volume":"107","author":"Bagattin","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41392-024-01756-w","article-title":"Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases","volume":"9","author":"Qian","year":"2024","journal-title":"Signal Transduct. Target. Ther."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/6\/895\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T01:21:18Z","timestamp":1781745678000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/6\/895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,17]]},"references-count":130,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["biom16060895"],"URL":"https:\/\/doi.org\/10.3390\/biom16060895","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,17]]}}}