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http://hdl.handle.net/2445/193158
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DC Field | Value | Language |
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dc.contributor.author | López Vicario, Cristina | - |
dc.contributor.author | Sebastián Muñoz, David | - |
dc.contributor.author | Casulleras, Mireia | - |
dc.contributor.author | Duran Güell, Marta | - |
dc.contributor.author | Flores Costa, Roger | - |
dc.contributor.author | Aguilar, Ferran | - |
dc.contributor.author | Lozano Salvatella, Juan José | - |
dc.contributor.author | Zhang, Ingrid W. | - |
dc.contributor.author | Titos Rodríguez, Esther | - |
dc.contributor.author | Kang, Jing X | - |
dc.contributor.author | Zorzano Olarte, Antonio | - |
dc.contributor.author | Arita, Makoto | - |
dc.contributor.author | Clària i Enrich, Joan | - |
dc.date.accessioned | 2023-02-06T17:31:54Z | - |
dc.date.available | 2023-07-05T05:10:23Z | - |
dc.date.issued | 2022-07-05 | - |
dc.identifier.issn | 0270-9139 | - |
dc.identifier.uri | http://hdl.handle.net/2445/193158 | - |
dc.description.abstract | Background and aim: Injury to hepatocyte mitochondria is common in metabolic dysfunction-associated fatty liver disease. Here, we investigated whether changes in the content of essential fatty acid-derived lipid autacoids affect hepatocyte mitochondrial bioenergetics and metabolic efficiency. Approach and results: The study was performed in transgenic mice for the fat-1 gene, which allows the endogenous replacement of the membrane omega-6-polyunsaturated fatty acid (PUFA) composition by omega-3-PUFA. Transmission electron microscopy revealed that hepatocyte mitochondria of fat-1 mice had more abundant intact cristae and higher mitochondrial aspect ratio. Fat-1 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. Fat-1 mice also showed increased mitofusin-2 and reduced dynamin-like protein 1 phosphorylation, which mediate mitochondrial fusion and fission, respectively. Mitochondria of fat-1 mice exhibited enhanced oxygen consumption rate, fatty acid β-oxidation, and energy substrate utilization as determined by high-resolution respirometry, [1-14 C]-oleate oxidation and nicotinamide adenine dinucleotide hydride/dihydroflavine-adenine dinucleotide production, respectively. Untargeted lipidomics identified a rich hepatic omega-3-PUFA composition and a specific docosahexaenoic acid (DHA)-enriched lipid fingerprint in fat-1 mice. Targeted lipidomics uncovered a higher content of DHA-derived lipid autacoids, namely resolvin D1 and maresin 1, which rescued hepatocytes from TNFα-induced mitochondrial dysfunction, and unblocked the tricarboxylic acid cycle flux and metabolic utilization of long-chain acyl-carnitines, amino acids, and carbohydrates. Importantly, fat-1 mice were protected against mitochondrial injury induced by obesogenic and fibrogenic insults. Conclusion: 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. | - |
dc.format.extent | 16 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Wiley | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1002/hep.32647 | - |
dc.relation.ispartof | Hepatology, 2022 | - |
dc.relation.uri | https://doi.org/10.1002/hep.32647 | - |
dc.rights | cc by-nc-nd (c) López-Vicario, Cristina et al., 2022 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.source | Articles publicats en revistes (Biomedicina) | - |
dc.subject.classification | Malalties del fetge | - |
dc.subject.classification | Àcids grassos | - |
dc.subject.classification | Membranes lipídiques | - |
dc.subject.classification | Àcids grassos omega-3 | - |
dc.subject.classification | Hormones | - |
dc.subject.other | Liver diseases | - |
dc.subject.other | Fatty acids | - |
dc.subject.other | Lipid membranes | - |
dc.subject.other | Omega-3 fatty acids | - |
dc.subject.other | Hormones | - |
dc.title | Essential lipid autacoids rewire mitochondrial energy efficiency in metabolic dysfunction-associated fatty liver disease | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 725762 | - |
dc.date.updated | 2023-02-06T17:31:54Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 35788956 | - |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Biomedicina) |
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725762.pdf | 15.09 MB | Adobe PDF | View/Open |
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