{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:42:39Z","timestamp":1786977759138,"version":"build-2736575974"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aim:<\/jats:title>\n                    <jats:p>Injury to hepatocyte mitochondria is common in metabolic dysfunction\u2010associated fatty liver disease. Here, we investigated whether changes in the content of essential fatty acid\u2013derived lipid autacoids affect hepatocyte mitochondrial bioenergetics and metabolic efficiency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results:<\/jats:title>\n                    <jats:p>\n                      The study was performed in transgenic mice for the\n                      <jats:italic toggle=\"yes\">fat\u20101<\/jats:italic>\n                      gene, which allows the endogenous replacement of the membrane omega\u20106\u2013polyunsaturated fatty acid (PUFA) composition by omega\u20103\u2013PUFA. Transmission electron microscopy revealed that hepatocyte mitochondria of\n                      <jats:italic toggle=\"yes\">fat\u20101<\/jats:italic>\n                      mice had more abundant intact cristae and higher mitochondrial aspect ratio.\n                      <jats:italic toggle=\"yes\">Fat\u20101<\/jats:italic>\n                      mice had increased expression of oxidative phosphorylation complexes I and II and translocases of both inner (translocase of inner mitochondrial membrane 44) and outer (translocase of the outer membrane 20) mitochondrial membranes.\n                      <jats:italic toggle=\"yes\">Fat\u20101<\/jats:italic>\n                      mice also showed increased mitofusin\u20102 and reduced dynamin\u2010like protein 1 phosphorylation, which mediate mitochondrial fusion and fission, respectively. Mitochondria of\n                      <jats:italic toggle=\"yes\">fat\u20101<\/jats:italic>\n                      mice exhibited enhanced oxygen consumption rate, fatty acid \u03b2\u2010oxidation, and energy substrate utilization as determined by high\u2010resolution respirometry, [1\u2010\n                      <jats:sup>14<\/jats:sup>\n                      C]\u2010oleate oxidation and nicotinamide adenine dinucleotide hydride\/dihydroflavine\u2010adenine dinucleotide production, respectively. Untargeted lipidomics identified a rich hepatic omega\u20103\u2013PUFA composition and a specific docosahexaenoic acid (DHA)\u2013enriched lipid fingerprint in\n                      <jats:italic toggle=\"yes\">fat\u20101<\/jats:italic>\n                      mice. Targeted lipidomics uncovered a higher content of DHA\u2010derived lipid autacoids, namely resolvin D1 and maresin 1, which rescued hepatocytes from TNF\u03b1\u2010induced mitochondrial dysfunction, and unblocked the tricarboxylic acid cycle flux and metabolic utilization of long\u2010chain acyl\u2010carnitines, amino acids, and carbohydrates. Importantly,\n                      <jats:italic toggle=\"yes\">fat\u20101<\/jats:italic>\n                      mice were protected against mitochondrial injury induced by obesogenic and fibrogenic insults.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our data uncover the importance of a lipid membrane composition rich in DHA and its lipid autacoid derivatives to have optimal hepatic mitochondrial and metabolic efficiency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.32647","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T09:14:01Z","timestamp":1657012441000},"page":"1303-1318","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":24,"title":["Essential lipid autacoids rewire mitochondrial energy efficiency in metabolic dysfunction\u2010associated fatty liver disease"],"prefix":"10.1097","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6609-8501","authenticated-orcid":false,"given":"Cristina","family":"L\u00f3pez\u2010Vicario","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Genetics Service, Hospital Cl\u00ednic, Institut D'Investigacions Biom\u00e8diques August Pi i Sunyer, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas, Barcelona, Spain"},{"name":"European Foundation for the Study of Chronic Liver Failure and Grifols Chair, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sebasti\u00e1n","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Departament de Bioqu\u00edmica i Biomedicina Molecular, University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2899-5826","authenticated-orcid":false,"given":"Mireia","family":"Casulleras","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Service, Hospital Cl\u00ednic, Institut D'Investigacions Biom\u00e8diques August Pi i Sunyer, Barcelona, Spain"},{"name":"European Foundation for the Study of Chronic Liver Failure and Grifols Chair, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3265-395X","authenticated-orcid":false,"given":"Marta","family":"Duran\u2010G\u00fcell","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Service, Hospital Cl\u00ednic, Institut D'Investigacions Biom\u00e8diques August Pi i Sunyer, Barcelona, Spain"},{"name":"European Foundation for the Study of Chronic Liver Failure and Grifols Chair, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8711-2552","authenticated-orcid":false,"given":"Roger","family":"Flores\u2010Costa","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Service, Hospital Cl\u00ednic, Institut D'Investigacions Biom\u00e8diques August Pi i Sunyer, Barcelona, Spain"},{"name":"European Foundation for the Study of Chronic Liver Failure and Grifols Chair, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferran","family":"Aguilar","sequence":"additional","affiliation":[{"name":"European Foundation for the Study of Chronic Liver Failure and Grifols Chair, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jos\u00e9","family":"Lozano","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6328-8257","authenticated-orcid":false,"given":"Ingrid W.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Service, Hospital Cl\u00ednic, Institut D'Investigacions Biom\u00e8diques August Pi i Sunyer, Barcelona, Spain"},{"name":"European Foundation for the Study of Chronic Liver Failure and Grifols Chair, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2543-2243","authenticated-orcid":false,"given":"Esther","family":"Titos","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Service, Hospital Cl\u00ednic, Institut D'Investigacions Biom\u00e8diques August Pi i Sunyer, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y 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