{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:08:34Z","timestamp":1787069314077,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK131038"],"award-info":[{"award-number":["R01DK131038"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03DK129419"],"award-info":[{"award-number":["R03DK129419"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CP19\/00098"],"award-info":[{"award-number":["CP19\/00098"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CP23\/00051"],"award-info":[{"award-number":["CP23\/00051"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FI21\/00003"],"award-info":[{"award-number":["FI21\/00003"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00505"],"award-info":[{"award-number":["PI20\/00505"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI23\/00171"],"award-info":[{"award-number":["PI23\/00171"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Metabolic dysfunction\u2010associated steatotic liver disease (MASLD) is a chronic liver condition that often progresses to more advanced stages, such as metabolic dysfunction\u2010associated steatohepatitis (MASH). MASH is characterized by inflammation and hepatocellular ballooning, in addition to hepatic steatosis. Despite the relatively high incidence of MASH in the population and its potential detrimental effects on human health, this liver disease is still not fully understood from a pathophysiological perspective. Deregulation of polyamine levels has been detected in various pathological conditions, including neurodegenerative diseases, inflammation, and cancer. However, the role of the polyamine pathway in chronic liver disorders such as MASLD has not been explored. In this study, we measured the expression of liver ornithine decarboxylase (ODC1), the rate\u2010limiting enzyme responsible for the production of putrescine, and the hepatic levels of putrescine, in a preclinical model of MASH as well as in liver biopsies of patients with obesity undergoing bariatric surgery. Our findings reveal that expression of ODC1 and the levels of putrescine, but not spermidine nor spermine, are elevated in hepatic tissue of both diet\u2010induced MASH mice and patients with biopsy\u2010proven MASH compared with control mice and patients without MASH, respectively. Furthermore, we found that the levels of putrescine were positively associated with higher aspartate aminotransferase concentrations in serum and an increased SAF score (steatosis, activity, fibrosis). Additionally, in\n                    <jats:italic>in vitro<\/jats:italic>\n                    assays using human HepG2 cells, we demonstrate that elevated levels of putrescine exacerbate the cellular response to palmitic acid, leading to decreased cell viability and increased release of CK\u201018. Our results support an association between the expression of ODC1 and the progression of MASLD, which could have translational relevance in understanding the onset of this disease. \u00a9 2024 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6330","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T04:09:21Z","timestamp":1721275761000},"page":"101-111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Increased hepatic putrescine levels as a new potential factor related to the progression of metabolic dysfunction\u2010associated steatotic liver disease"],"prefix":"10.1002","volume":"264","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8938-2767","authenticated-orcid":false,"given":"Mar\u00eda \u00c1ngeles","family":"N\u00fa\u00f1ez\u2010S\u00e1nchez","sequence":"first","affiliation":[{"name":"Obesity, Diabetes and Metabolism Laboratory Biomedical Research Institute of Murcia (IMIB)  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9750-4237","authenticated-orcid":false,"given":"Mar\u00eda Antonia","family":"Mart\u00ednez\u2010S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Obesity, Diabetes and Metabolism Laboratory Biomedical Research Institute of Murcia (IMIB)  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1904-7859","authenticated-orcid":false,"given":"Marta","family":"Sierra\u2010Cruz","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine University of Illinois  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5616-2218","authenticated-orcid":false,"given":"Ana","family":"Lambertos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology B and Immunology, Faculty of Medicine University of Murcia  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4490-1866","authenticated-orcid":false,"given":"Sara","family":"Rico\u2010Chazarra","sequence":"additional","affiliation":[{"name":"Obesity, Diabetes and Metabolism Laboratory Biomedical Research Institute of Murcia (IMIB)  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9308-1043","authenticated-orcid":false,"given":"Alba","family":"Oliva\u2010Bolar\u00edn","sequence":"additional","affiliation":[{"name":"Obesity, Diabetes and Metabolism Laboratory Biomedical Research Institute of Murcia (IMIB)  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5297-0194","authenticated-orcid":false,"given":"Andr\u00e9s","family":"Balaguer\u2010Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Obesity, Diabetes and Metabolism Laboratory Biomedical Research Institute of Murcia (IMIB)  Murcia Spain"},{"name":"Department of General and Digestive System Surgery Virgen de la Arrixaca University Hospital  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9847-0275","authenticated-orcid":false,"given":"Jos\u00e9 Enrique","family":"Yuste","sequence":"additional","affiliation":[{"name":"Metabolomics Platform of CEBAS\u2010CSIC Campus Universitario de Espinardo  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3307-1326","authenticated-orcid":false,"given":"Carlos Manuel","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Experimental Pathology Platform Biomedical Research Institute of Murcia (IMIB)  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2877-5652","authenticated-orcid":false,"given":"Adriana","family":"Mika","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Faculty of Pharmacy Medical University of Gdansk  Gdansk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Dolores","family":"Frutos","sequence":"additional","affiliation":[{"name":"Department of General and Digestive System Surgery Virgen de la Arrixaca University Hospital  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo J","family":"Llamoza\u2010Torres","sequence":"additional","affiliation":[{"name":"Obesity, Diabetes and Metabolism Laboratory Biomedical Research Institute of Murcia (IMIB)  Murcia Spain"},{"name":"Division of Liver Diseases, Department of Gastroenterology and Hepatology University Clinical Hospital Virgen de la Arrixaca  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8787-2706","authenticated-orcid":false,"given":"Jos\u00e9","family":"C\u00f3rdoba\u2010Chac\u00f3n","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine University of Illinois  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6804-5449","authenticated-orcid":false,"given":"Bruno","family":"Ramos\u2010Molina","sequence":"additional","affiliation":[{"name":"Obesity, Diabetes and Metabolism Laboratory Biomedical Research Institute of Murcia (IMIB)  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.109"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.10.033"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.2298"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32511-3"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R116.731661"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100361"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R500031200"},{"key":"e_1_2_8_9_1","first-page":"615","article-title":"The influence of desipramine on the blood pressure elevation and heart rate stimulation by levonordefrin and felypressin alone and in the presence of local anaesthetics","volume":"41","author":"Dreyer AC","year":"1986","journal-title":"J Dent Assoc S Afr"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)11301-C"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.12.016"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101261"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2019.00024"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2021.01.003"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04629-z"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00514.2010"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00420.2014"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25889"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)64849-5"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.23711"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2017.11.006"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2018.04.008"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15059"},{"key":"e_1_2_8_24_1","first-page":"214","article-title":"The mechanism of hepatoprotection by epsilon aminocaproic acid and putrescine","volume":"96","author":"Putnam CW","year":"1984","journal-title":"Surgery"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365529409090457"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-004-0549-0"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-011-0946-7"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1159\/000497434"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00431.2011"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo10040168"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15558"},{"key":"e_1_2_8_32_1","article-title":"Restoring polyamine levels by supplementation of spermidine modulates hepatic immune landscape in murine model of NASH","volume":"2023","author":"Szydlowska M","year":"1869","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.09.078"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118739"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202100315"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c02729"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32788-x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.TM118.003339"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/14.5.1077"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-32659-w"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.5604\/16652681.1171767"},{"key":"e_1_2_8_42_1","first-page":"471","article-title":"Ability of several hexachlorobenzene metabolites to decrease rat\u2010liver porphyrinogen carboxy\u2010lyase and to produce porphyrin accumulation in chick\u2010embryo liver","author":"Billi SC","year":"1986","journal-title":"IARC Sci Publ"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840200512"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0239-3_17"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.6330","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:24:52Z","timestamp":1761053092000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.6330"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,18]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/path.6330"],"URL":"https:\/\/doi.org\/10.1002\/path.6330","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,18]]},"assertion":[{"value":"2024-01-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}