{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:53:56Z","timestamp":1792065236692,"version":"4.4.0"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["569468610 (GE 2217\/4-1)"],"award-info":[{"award-number":["569468610 (GE 2217\/4-1)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004403","name":"Th\u00fcringer Aufbaubank","doi-asserted-by":"publisher","award":["2023 FGR 0077 (FSU), 2023 FGR 0078 (UKJ)"],"award-info":[{"award-number":["2023 FGR 0077 (FSU), 2023 FGR 0078 (UKJ)"]}],"id":[{"id":"10.13039\/501100004403","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012957","name":"Friedrich-Schiller-Universit\u00e4t Jena","doi-asserted-by":"publisher","award":["21.3-PC\/2023-04."],"award-info":[{"award-number":["21.3-PC\/2023-04."]}],"id":[{"id":"10.13039\/100012957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Metabolic dysfunction-associated steatohepatitis (MASH) represents a critical progression of metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by hepatic steatosis, inflammation, and beginning fibrosis. The selection of appropriate animal models is crucial for understanding disease mechanisms and evaluating therapeutic interventions. While wild-type C57BL\/6 mice are widely used, hyperlipidemic apolipoprotein E-deficient (\n                      <jats:italic>Apoe<\/jats:italic>\n                      <jats:sup>-\/-<\/jats:sup>\n                      ) mice may offer superior disease modeling capabilities. This study compared the development and progression of diet-induced MASH in\n                      <jats:italic>Apoe<\/jats:italic>\n                      <jats:sup>-\/-<\/jats:sup>\n                      mice versus wild-type C57BL\/6J mice over multiple time points, with a focus on inflammatory responses and histological changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male wild-type C57BL\/6J and male\n                      <jats:italic>Apoe<\/jats:italic>\n                      <jats:sup>-\/-<\/jats:sup>\n                      mice were fed either standard chow diet or high-fat\/high-fructose (Hf\/Hf) diet for 8, 12, 16, or 24 weeks. Comprehensive analyses included histological evaluation, MRS based fat quantification, immunohistochemistry, serum biochemistry, cytokine profiling, trace element analysis, oxylipin profiling by UPLC-MS\/MS, intestinal barrier function assessment, and gene expression analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Apoe<\/jats:italic>\n                      <jats:sup>-\/-<\/jats:sup>\n                      mice showed markedly accelerated MASH development compared to wild-type mice. Notably,\n                      <jats:italic>Apoe<\/jats:italic>\n                      <jats:sup>-\/-<\/jats:sup>\n                      mice fed Hf\/Hf diet for 12 weeks exhibited substantially greater inflammatory infiltration than wild-type mice even after 24 weeks of Hf\/Hf diet. This enhanced inflammatory response was accompanied by increased infiltration of macrophages (CD68\n                      <jats:sup>+<\/jats:sup>\n                      cells), elevated levels of pro-inflammatory cytokines, altered trace element homeostasis, and dysregulated oxylipin profiles favoring pro-inflammatory mediators. There was also evidence of compromised intestinal barrier function and more pronounced histological features of MASH, including steatosis, lobular inflammation and hepatocyte ballooning.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Apoe<\/jats:italic>\n                      <jats:sup>-\/-<\/jats:sup>\n                      mice represent a superior model for MASH research, demonstrating accelerated disease progression and enhanced inflammatory responses compared to the wild-type mice. The rapid and robust inflammatory phenotype in\n                      <jats:italic>Apoe<\/jats:italic>\n                      <jats:sup>-\/-<\/jats:sup>\n                      mice provides a more efficient and clinically relevant model for investigating MASH pathogenesis and testing therapeutic interventions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1895809","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T04:23:52Z","timestamp":1784262232000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Superior inflammatory response and MASH progression in Apoe-\/- mice compared to wild-type mice: a comprehensive time-course analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Anja R.","family":"Geisler","sequence":"first","affiliation":[{"name":"Institute of Nutritional Science, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Meinhardt","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Science, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Otto","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Science, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Hupfer","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Science, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty","family":"Hebecker","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Science, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bill J.","family":"Perkowski","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Werner","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Ting","family":"Zhao","sequence":"additional","affiliation":[{"name":"Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Ebert","sequence":"additional","affiliation":[{"name":"MVZ Medical Laboratories Dessau Kassel GmbH","place":["Dessau, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Burghoff","sequence":"additional","affiliation":[{"name":"MVZ Medical Laboratories Dessau Kassel GmbH","place":["Dessau, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen R.","family":"Reichenbach","sequence":"additional","affiliation":[{"name":"Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Gerdes","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf","place":["D\u00fcsseldorf, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Werz","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna P.","family":"Kipp","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Science, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Lorkowski","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Science, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Witt-Wallert","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Science, Friedrich Schiller University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(26)00011-7","article-title":"Global burden of metabolic dysfunction-associated steatotic liver disease, 1990\u20132023, and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2023","volume":"11","author":"Kim","year":"2026","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2902351","article-title":"An overview of murine high fat diet as a model for type 2 diabetes mellitus","volume":"2016","author":"Heydemann","year":"2016","journal-title":"J Diabetes Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-024-01043-6","article-title":"An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD)","volume":"6","author":"Vacca","year":"2024","journal-title":"Nat Metab"},{"key":"B7","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1002\/path.4829","article-title":"Animal models of non-alcoholic fatty liver disease: current perspectives and recent advances","volume":"241","author":"Lau","year":"2017","journal-title":"J Pathol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/science.1411543","article-title":"Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E","volume":"258","author":"Zhang","year":"1992","journal-title":"Science"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/srep12931","article-title":"Seven weeks of Western diet in apolipoprotein-E-deficient mice induce metabolic syndrome and non-alcoholic steatohepatitis with liver fibrosis","volume":"5","author":"Schierwagen","year":"2015","journal-title":"Sci Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-016-1427-y","article-title":"Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders","volume":"94","author":"Mahley","year":"2016","journal-title":"J Mol Med Berl Ger"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90362-g","article-title":"Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in E S cells","volume":"71","author":"Plump","year":"1992","journal-title":"Cell"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0145-7","article-title":"From NASH to HCC: current concepts and future challenges","volume":"16","author":"Anstee","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03345-4","article-title":"Burdens of type 2 diabetes and cardiovascular disease attributable to sugar-sweetened beverages in 184 countries","volume":"31","author":"Lara-Castor","year":"2025","journal-title":"Nat Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2015.10.027","article-title":"A \u201csystems medicine\u201d approach to the study of non-alcoholic fatty liver disease","volume":"48","author":"Petta","year":"2016","journal-title":"Dig Liver Dis"},{"key":"B15","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/978-3-319-59180-3_10","article-title":"Dietary patterns, foods, nutrients and phytochemicals in non-alcoholic fatty liver disease","volume-title":"Dietary Patterns and Whole Plant Foods in Aging and Disease","author":"Dreher","year":"2018"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/137579","article-title":"Lipotoxicity: effects of dietary saturated and transfatty acids","volume":"2013","author":"Estadella","year":"2013","journal-title":"Mediators Inflammation"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M001230","article-title":"Western diet changes cardiac acyl-CoA composition in obese rats: a potential role for hepatic lipogenesis","volume":"51","author":"Harmancey","year":"2010","journal-title":"J Lipid Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatol Baltim Md"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.17504\/protocols.io.81wgb6j1olpk\/v1","article-title":"Histological image quantification of picrosirius red stained skeletal muscle sections v1","author":"Hildyard","year":"2022"},{"key":"B20","doi-asserted-by":"publisher","first-page":"3479","DOI":"10.1038\/s41467-023-39245-3","article-title":"Excessive copper impairs intrahepatocyte trafficking and secretion of selenoprotein P","volume":"14","author":"Schwarz","year":"2023","journal-title":"Nat Commun"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2025.103963","article-title":"Distribution interactions of the trace elements zinc, copper, and selenium under conditions of their parallel deficiency","volume":"89","author":"Lossow","year":"2026","journal-title":"Redox Biol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/s12263-010-0168-8","article-title":"Nrf2 target genes are induced under marginal selenium-deficiency","volume":"5","author":"M\u00fcller","year":"2010","journal-title":"Genes Nutr"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2023.127167","article-title":"Measurement of trace elements in murine liver tissue samples: Comparison between ICP-MS\/MS and TXRF","volume":"78","author":"Lossow","year":"2023","journal-title":"J Trace Elem Med Biol Organ Soc Miner Trace Elem GMS"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910300604","article-title":"Estimation of metabolite concentrations from localized in vivo proton NMRSpectra","volume":"30","author":"Provencher","year":"1993","journal-title":"Magn Reson Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.698","article-title":"Automatic quantitation of localized in vivo1 H spectra with LCModel","volume":"14","author":"Provencher","year":"2001","journal-title":"NMR BioMed"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.24657","article-title":"Fat quantification using multiecho sequences with bipolar gradients: Investigation of accuracy and noise performance","volume":"71","author":"Peterson","year":"2014","journal-title":"Magn Reson Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.1622","article-title":"In vivo characterization of the liver fat 1H MRSpectrum","volume":"24","author":"Hamilton","year":"2011","journal-title":"NMR BioMed"},{"key":"B28","first-page":"1713","volume-title":"Fast 3D isotropic high-resolution MRI of mouse brain using a variable flip angle RARE sequence with T2 compensation @9.4T","author":"Hung","year":""},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201802509R","article-title":"Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome","volume":"33","author":"Werner","year":"2019","journal-title":"FASEB J"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.06.003","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"79","author":"Rinella","year":"2023","journal-title":"J Hepatol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/srep24399","article-title":"A pharmacological inhibitor of NLRP3 inflammasome prevents non-alcoholic fatty liver disease in a mouse model induced by high fat diet","volume":"6","author":"Yang","year":"2016","journal-title":"Sci Rep"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201700915","article-title":"High fat diets composed of palmstearin and olive oil equally exacerbate liver inflammatory damage and metabolic stress in mice","volume":"62","author":"Meidan","year":"2018","journal-title":"Mol Nutr Food Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2024.109711","article-title":"Treatment with 1.25% cholesterol enriched diet produces severe fatty liver disease characterized by advanced fibrosis and inflammation and impaired autophagy in mice","volume":"134","author":"Taberner-Cort\u00e9s","year":"2024","journal-title":"J Nutr Biochem"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26429","article-title":"Macrophage plasticity, polarization, and function in health and disease","volume":"233","author":"Shapouri\u2010Moghaddam","year":"2018","journal-title":"J Cell Physiol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175336","article-title":"Impact of human monocyte and macrophage polarization on NLR expression and NLRP3 inflammasome activation","volume":"12","author":"Awad","year":"2017","journal-title":"PLo S One"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700630","article-title":"Role of STAT3 in liver regeneration: survival, DNASynthesis, inflammatory reaction and liver mass recovery","volume":"87","author":"Moh","year":"2007","journal-title":"Lab Invest"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2020.1761203","article-title":"Different roles of interleukin 6 and interleukin 11 in the liver: implications for therapy","volume":"16","author":"Widjaja","year":"2020","journal-title":"Hum Vaccines Immunother"},{"key":"B38","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s40164-024-00527-1","article-title":"The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases","volume":"13","author":"Wang","year":"2024","journal-title":"Exp Hematol Oncol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2006.01750.x","article-title":"Interleukin\u20106 trans\u2010signalling in chronic inflammation and cancer","volume":"63","author":"Scheller","year":"2006","journal-title":"Scand J Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.14201","article-title":"Making sense of IL\u20106 signalling cues in pathophysiology","volume":"596","author":"Millrine","year":"2022","journal-title":"FEB S Lett"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1865-y","article-title":"Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance","volume":"53","author":"Matthews","year":"2010","journal-title":"Diabetologia"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.02.105","article-title":"Involvement of STAT3-regulated hepatic soluble factors in attenuation of stellate cell activity and liver fibrogenesis in mice","volume":"406","author":"Shigekawa","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.4.1243","article-title":"Defective inflammatory response in interleukin 6-deficient mice","volume":"180","author":"Fattori","year":"1994","journal-title":"J Exp Med"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.6.3745-3748.2005","article-title":"Endogenous interleukin-6 plays a crucial protective role in streptococcal toxic shock syndrome via suppression of tumor necrosis factor alpha production","volume":"73","author":"Diao","year":"2005","journal-title":"Infect Immun"},{"key":"B45","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.trsl.2018.07.014","article-title":"Mitochondria in innate immune signaling","volume":"202","author":"Banoth","year":"2018","journal-title":"Transl Res"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3390\/cimb44100320","article-title":"Western diet-fed ApoE knockout male mice as an experimental model of non-alcoholic steatohepatitis","volume":"44","author":"Camargo","year":"2022","journal-title":"Curr Issues Mol Biol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2018.08.107","article-title":"Role of activating transcription factor 3 and its interacting proteins under physiological and pathological conditions","volume":"120","author":"Rohini","year":"2018","journal-title":"Int J Biol Macromol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.2337\/db21-0181","article-title":"Hepatocytic activating transcription factor 3 protects against steatohepatitis via hepatocyte nuclear factor 4\u03b1","volume":"70","author":"Xu","year":"2021","journal-title":"Diabetes"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.023","article-title":"Activating transcription factor 3 is a target molecule linking hepatic steatosis to impaired glucose homeostasis","volume":"67","author":"Kim","year":"2017","journal-title":"J Hepatol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3390\/stresses2010005","article-title":"The nitration of proteins, lipids and DNA by peroxynitrite derivatives-chemistry involved and biological relevance","volume":"2","author":"P\u00e9rez De La Lastra","year":"2022","journal-title":"Stresses"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00304.2014","article-title":"Hepatic TLR4 signaling in obese NAFLD","volume":"309","author":"Sharifnia","year":"2015","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"68","DOI":"10.3390\/livers1020007","article-title":"The impact of the NLRP3 pathway in the pathogenesis of non-alcoholic fatty liver disease and alcohol-related liver disease","volume":"1","author":"Sheriff","year":"2021","journal-title":"Livers"},{"key":"B53","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-981-10-8684-7_3","article-title":"Pathogenesis of NASH: How metabolic complications of overnutrition favour lipotoxicity and pro-inflammatory fatty liver disease","volume-title":"Obesity, Fatty Liver and Liver Cancer","author":"Farrell","year":"2018"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2012.11.002","article-title":"Cholesterol metabolism and the pathogenesis of non-alcoholic steatohepatitis","volume":"52","author":"Musso","year":"2013","journal-title":"Prog Lipid Res"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.222745","article-title":"Apolipoprotein E induces antiinflammatory phenotype in macrophages","volume":"31","author":"Baitsch","year":"2011","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"e1-e11","DOI":"10.1161\/CIRCRESAHA.117.305844","article-title":"Apolipoprotein E enhances microRNA-146a in monocytes and macrophages to suppress nuclear factor-\u03baB\u2013driven inflammation and atherosclerosis","volume":"117","author":"Li","year":"2015","journal-title":"Circ Res"},{"key":"B57","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1042\/BJ20100016","article-title":"Apolipoprotein E inhibits Toll-like receptor (TLR)-3- and TLR-4-mediated macrophage activation through distinct mechanisms","volume":"428","author":"Zhu","year":"2010","journal-title":"Biochem J"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116702","article-title":"Chronic iron overload intensifies atherosclerosis in apolipoprotein E deficient mice: Role of oxidative stress and endothelial dysfunction","volume":"233","author":"Marques","year":"2019","journal-title":"Life Sci"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2025.02.017","article-title":"Regular exercise alleviates metabolic dysfunction-associated steatohepatitis through rescuing mitochondrial oxidative stress and dysfunction in liver","volume":"230","author":"Lin","year":"2025","journal-title":"Free Radic Biol Med"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2011.04.013","article-title":"The role of oxidative stress in non-alcoholic steatohepatitis","volume":"412","author":"Koek","year":"2011","journal-title":"Clin Chim Acta"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2007.06.013","article-title":"Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells","volume":"85","author":"Yang","year":"2007","journal-title":"Exp Eye Res"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.711227","article-title":"Role of copper on mitochondrial function and metabolism","volume":"8","author":"Ruiz","year":"2021","journal-title":"Front Mol Biosci"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.170","article-title":"A role for low hepatic copper concentrations in nonalcoholic fatty liver disease","volume":"105","author":"Aigner","year":"2010","journal-title":"Am J Gastroenterol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1016\/j.jnutbio.2015.04.009","article-title":"Nutrigenomics analysis reveals that copper deficiency and dietary sucrose up-regulate inflammation, fibrosis and lipogenic pathways in a mature rat model of nonalcoholic fatty liver disease","volume":"26","author":"Tallino","year":"2015","journal-title":"J Nutr Biochem"},{"key":"B65","doi-asserted-by":"publisher","first-page":"33","DOI":"10.20517\/mtod.2024.47","article-title":"Copper and liver fibrosis in MASLD: The two-edged sword of copper deficiency and toxicity","volume":"4","author":"Lonardo","year":"2024","journal-title":"Metab Tgt Organ Damage"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-013-9725-5","article-title":"The alteration of copper homeostasis in inflammation induced by lipopolysaccharides","volume":"154","author":"Han","year":"2013","journal-title":"Biol Trace Elem Res"},{"key":"B67","doi-asserted-by":"publisher","first-page":"60","DOI":"10.5633\/amm.2022.0208","article-title":"Blue moonlighting in the immune response: Roles of copper and ceruloplasmin in the pathogenesis of inflammation and immune-mediated diseases","volume":"61","author":"Milenkovi\u0107","year":"2022","journal-title":"Acta Med Median"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24282","article-title":"Copper\/MYC\/CTR1 interplay: A dangerous relationship in hepatocellular carcinoma","volume":"9","author":"Porcu","year":"2018","journal-title":"Oncotarget"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jnutbio.2015.08.024","article-title":"Nutritional therapy for nonalcoholic fatty liver disease","volume":"29","author":"Dongiovanni","year":"2016","journal-title":"J Nutr Biochem"},{"key":"B70","doi-asserted-by":"publisher","first-page":"e0802","DOI":"10.1097\/HC9.0000000000000802","article-title":"Arachidonic acid metabolism in metabolic dysfunction\u2013associated steatotic liver disease and liver fibrosis","volume":"9","author":"Ma","year":"2025","journal-title":"Hepatol Commun"},{"key":"B71","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2010.07565.x","article-title":"Pronounced adipogenesis and increased insulin sensitivity caused by overproduction of prostaglandin D2in vivo","volume":"277","author":"Fujitani","year":"2010","journal-title":"FEB S J"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2023.106772","article-title":"Prostaglandin D2 regulates Escherichia coli-induced inflammatory responses through TLR2, TLR4, and NLRP3 in macrophages","volume":"169","author":"Gong","year":"2023","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01525-18","article-title":"Dietary fatty acids sustain the growth of the human gut microbiota","volume":"84","author":"Agans","year":"2018","journal-title":"Appl Environ Microbiol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3945\/jn.116.242859","article-title":"Intestinal barrier function and the gut microbiome are differentially affected in mice fed a Western-style diet or drinking water supplemented with fructose","volume":"147","author":"Volynets","year":"2017","journal-title":"J Nutr"},{"key":"B76","doi-asserted-by":"publisher","first-page":"H216-H222","DOI":"10.1111\/1750-3841.13166","article-title":"High\u2010fat diet\u2010induced intestinal hyperpermeability is associated with increased bile acids in the large intestine of mice","volume":"81","author":"Murakami","year":"2016","journal-title":"J Food Sci"},{"key":"B77","doi-asserted-by":"publisher","first-page":"3434","DOI":"10.1038\/s41467-025-58649-x","article-title":"Balance between bile acid conjugation and hydrolysis activity can alter outcomes of gut inflammation","volume":"16","author":"Fu","year":"2025","journal-title":"Nat Commun"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2023.109434","article-title":"The chronic consumption of dietary fructose promotes the gut Clostridium species imbalance and bile acid alterations in developing nonalcoholic fatty liver disease","volume":"121","author":"Zhang","year":"2023","journal-title":"J Nutr Biochem"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2021.100387","article-title":"Bile acids contribute to the development of non-alcoholic steatohepatitis in mice","volume":"4","author":"Gillard","year":"2022","journal-title":"JHEP Rep"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00029.2015","article-title":"Changes in intestinal barrier function and gut microbiota in high-fat diet-fed rats are dynamic and region dependent","volume":"308","author":"Hamilton","year":"2015","journal-title":"Am J Physiol-Gastrointest Liver Physiol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2020.09.008","article-title":"Dietary fructose alters the composition, localization, and metabolism of gut microbiota in association with worsening colitis","volume":"11","author":"Montrose","year":"2021","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2017.01.010","article-title":"Chronic administration of saturated fats and fructose differently affect SREBP activity resulting in different modulation of Nrf2 and Nlrp3 inflammasome pathways in mice liver","volume":"42","author":"Nigro","year":"2017","journal-title":"J Nutr Biochem"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2023.109307","article-title":"Associations of altered hepatic gene expression in American lifestyle-induced obesity syndrome diet-fed mice with metabolic changes during NAFLD development and progression","volume":"115","author":"Iannone","year":"2023","journal-title":"J Nutr Biochem"},{"key":"B84","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1186\/s12866-024-03663-0","article-title":"Gut microbiota and mycobiota change with feeding duration in mice on a high-fat and high-fructose diet","volume":"24","author":"Zheng","year":"2024","journal-title":"BMC Microbiol"},{"key":"B85","doi-asserted-by":"publisher","first-page":"89723","DOI":"10.5662\/wjm.v14.i1.89723","article-title":"Time-dependent impact of a high-fat diet on the intestinal barrier of male mice","volume":"14","author":"Miranda","year":"2024","journal-title":"World J Methodol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100738","article-title":"High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL\/6j mice","volume":"7","author":"Van Der Heijden","year":"2015","journal-title":"Aging"},{"key":"B87","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s12986-023-00749-w","article-title":"A high-trans fat, high-carbohydrate, high-cholesterol, high-cholate diet-induced nonalcoholic steatohepatitis mouse model and its hepatic immune response","volume":"20","author":"Zhang","year":"2023","journal-title":"Nutr Metab"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-005-2997-0","article-title":"Feeding apolipoprotein E-knockout mice with cholesterol and fat enriched diets may be a model of non-alcoholic steatohepatitis","volume":"268","author":"Tous","year":"2005","journal-title":"Mol Cell Biochem"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.2147\/jir.s343236","article-title":"Melatonin suppresses NLRP3 inflammasome activation via TLR4\/NF-\u03baB and P2X7R signaling in high-fat diet-induced murine NASH model","volume":"15","author":"Saha","year":"2022","journal-title":"J Inflammation Res"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2022.109217","article-title":"Chronic high-fat diet induces galectin-3 and TLR4 to activate NLRP3 inflammasome in NASH","volume":"112","author":"Li","year":"2023","journal-title":"J Nutr Biochem"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.17269\/s41997-025-01025-5","article-title":"Sex differences in the prevalence and cardiometabolic risk profiles of steatotic liver disease: A Canadian Longitudinal Study on Aging analysis","volume":"117","author":"Burnside","year":"2025","journal-title":"Can J Public Health"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1567573","article-title":"Sex differences in diet-induced MASLD \u2013 are female mice naturally protected","volume":"16","author":"Meyer","year":"2025","journal-title":"Front Endocrinol"},{"key":"B93","doi-asserted-by":"publisher","first-page":"101222","DOI":"10.1016\/j.jhepr.2024.101222","article-title":"Sex differences in murine MASH induced by a fructose-palmitate-cholesterol-enriched diet","volume":"7","author":"Arivazhagan","year":"2025","journal-title":"JHEP Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1895809\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:11:09Z","timestamp":1792062669000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1895809\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":93,"alternative-id":["10.3389\/fimmu.2026.1895809"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1895809","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]},"article-number":"1895809"}}