{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T06:12:23Z","timestamp":1781590343970,"version":"3.54.5"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>The liver plays a central role in all metabolic processes in the body. However, precise characterization of liver metabolism is often obscured by its inherent complexity. Phosphorylated metabolites occupy a prominent position in all anabolic and catabolic pathways. Here, we develop a <jats:sup>31<\/jats:sup>P nuclear magnetic resonance (NMR)\u2013based method to study the liver \u201cphosphorome\u201d through the simultaneous identification and quantification of multiple hydrophilic and hydrophobic phosphorylated metabolites.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We applied this technique to define the metabolic landscape in livers from a mouse model of the rare disease disorder congenital erythropoietic porphyria (CEP) as well as two well\u2010known murine models of nonalcoholic steatohepatitis: one genetic, methionine adenosyltransferase 1A knockout mice, and the other dietary, mice fed a high\u2010fat choline\u2010deficient diet. We report alterations in the concentrations of phosphorylated metabolites that are readouts of the balance between glycolysis, gluconeogenesis, the pentose phosphate pathway, the tricarboxylic acid cycle, and oxidative phosphorylation and of phospholipid metabolism and apoptosis. Moreover, these changes correlate with the main histological features: steatosis, apoptosis, iron deposits, and fibrosis. Strikingly, treatment with the repurposed drug ciclopirox improves the phosphoromic profile of CEP mice, an effect that was mirrored by the normalization of liver histology.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In conclusion, these findings indicate that NMR\u2010based phosphoromics may be used to unravel metabolic phenotypes of liver injury and to identify the mechanism of drug action.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31676","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T11:44:18Z","timestamp":1607341458000},"page":"148-163","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":25,"title":["Metabolic Landscape of the Mouse Liver by Quantitative 31P Nuclear Magnetic Resonance Analysis of the Phosphorome"],"prefix":"10.1097","volume":"74","author":[{"given":"Ganeko","family":"Bernardo\u2010Seisdedos","sequence":"first","affiliation":[{"name":"Precision Medicine and Metabolism Laboratory,CIC bioGUNE,Basque Research and Technology Alliance,Parque Tecnol\u00f3gico de Bizkaia,Derio,Spain"},{"name":"ATLAS Molecular Pharma S. L.,Derio,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Bilbao","sequence":"additional","affiliation":[{"name":"Precision Medicine and Metabolism Laboratory,CIC bioGUNE,Basque Research and Technology Alliance,Parque Tecnol\u00f3gico de Bizkaia,Derio,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fern\u00e1ndez\u2010Ramos","sequence":"additional","affiliation":[{"name":"Precision Medicine and Metabolism Laboratory,CIC bioGUNE,Basque Research and Technology Alliance,Parque Tecnol\u00f3gico de Bizkaia,Derio,Spain"},{"name":"CIBERehd,Instituto de Salud Carlos III,Madrid,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Lopitz\u2010Otsoa","sequence":"additional","affiliation":[{"name":"Precision Medicine and Metabolism Laboratory,CIC bioGUNE,Basque Research and Technology Alliance,Parque Tecnol\u00f3gico de Bizkaia,Derio,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Gutierrez de Juan","sequence":"additional","affiliation":[{"name":"Precision Medicine and Metabolism Laboratory,CIC bioGUNE,Basque Research and Technology Alliance,Parque Tecnol\u00f3gico de Bizkaia,Derio,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maider","family":"Bizkarguenaga","sequence":"additional","affiliation":[{"name":"Precision Medicine and Metabolism Laboratory,CIC bioGUNE,Basque Research and Technology Alliance,Parque Tecnol\u00f3gico de Bizkaia,Derio,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borja","family":"Mateos","sequence":"additional","affiliation":[{"name":"Precision Medicine and Metabolism Laboratory,CIC bioGUNE,Basque Research and Technology Alliance,Parque Tecnol\u00f3gico de Bizkaia,Derio,Spain"},{"name":"Department of Structural and Computational Biology,University of Vienna,Max Perutz Labs,Vienna Biocenter Campus 5,Vienna,Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5099-3421","authenticated-orcid":false,"given":"Marcos F.","family":"Fondevila","sequence":"additional","affiliation":[{"name":"Department of Physiology,CIMUS,University of Santiago de Compostela\u2010Instituto de Investigaci\u00f3n Sanitaria,Santiago de Compostela,Spain"},{"name":"CIBER Fisiopatologia de la Obesidad y Nutrici\u00f3n (CIBERobn),Santiago de Compostela,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5871-4052","authenticated-orcid":false,"given":"Jordi","family":"Abril\u2010Fornaguera","sequence":"additional","affiliation":[{"name":"Liver Cancer Translational Research Laboratory,Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS),Hospital Cl\u00ednic,Universitat de Barcelona,Barcelona,Catalonia,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammo","family":"Diercks","sequence":"additional","affiliation":[{"name":"NMR Platform,CIC bioGUNE,Basque Research and Technology Alliance,Parque Tecnol\u00f3gico de Bizkaia,Bizkaia,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelly C.","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Digestive and Liver Diseases,Department of Medicine,Cedars\u2010Sinai Medical Center,Los Angeles,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rub\u00e9n","family":"Nogueiras","sequence":"additional","affiliation":[{"name":"Department of Physiology,CIMUS,University of Santiago de Compostela\u2010Instituto de Investigaci\u00f3n Sanitaria,Santiago de Compostela,Spain"},{"name":"CIBER Fisiopatologia de la Obesidad y Nutrici\u00f3n (CIBERobn),Santiago de Compostela,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Mato","sequence":"additional","affiliation":[{"name":"Precision Medicine and Metabolism Laboratory,CIC bioGUNE,Basque Research and Technology Alliance,Parque Tecnol\u00f3gico de Bizkaia,Derio,Spain"},{"name":"CIBERehd,Instituto de Salud Carlos III,Madrid,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8748-4105","authenticated-orcid":false,"given":"Oscar","family":"Millet","sequence":"additional","affiliation":[{"name":"Precision Medicine and Metabolism Laboratory,CIC bioGUNE,Basque Research and Technology Alliance,Parque Tecnol\u00f3gico de Bizkaia,Derio,Spain"},{"name":"ATLAS Molecular Pharma S. 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