Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles
dc.contributor.author | Martínez Arranz, Ibon | |
dc.contributor.author | Bruzzone, Chiara | |
dc.contributor.author | Noureddin, Mazen | |
dc.contributor.author | Gil Redondo, Rubén | |
dc.contributor.author | Mincholé, Itziar | |
dc.contributor.author | Bizkarguenaga, Maider | |
dc.contributor.author | Arretxe Oliden, Enara | |
dc.contributor.author | Iruarrizaga Lejarreta, Marta | |
dc.contributor.author | Fernández Ramos, David | |
dc.contributor.author | Lopitz Otsoa, Fernando | |
dc.contributor.author | Mayo, Rebeca | |
dc.contributor.author | Embade, Nieves | |
dc.contributor.author | Newberry, Elizabeth | |
dc.contributor.author | Mittendorf, Bettina | |
dc.contributor.author | Izquierdo Sánchez, Laura | |
dc.contributor.author | Smid, Vaclav | |
dc.contributor.author | Arnold, Jorge | |
dc.contributor.author | Iruzubieta, Paula | |
dc.contributor.author | Pérez Castaño, Ylenia | |
dc.contributor.author | Krawczyk, Marcin | |
dc.contributor.author | Martínez de Marigorta Izaga, Edorta | |
dc.contributor.author | Morrison, Martine C. | |
dc.contributor.author | Kleemann, Robert | |
dc.contributor.author | Martín Duce, Antonio | |
dc.contributor.author | Hayardeny, Liat | |
dc.contributor.author | Vitek, Libor | |
dc.contributor.author | Bruha, Radan | |
dc.contributor.author | Aller de la Fuente, Rocio | |
dc.contributor.author | Crespo, Javier | |
dc.contributor.author | Romero Gómez, Manuel | |
dc.contributor.author | Bañales Asurmendi, Jesús María | |
dc.contributor.author | Arrese, Marco | |
dc.contributor.author | Cusi, Kenneth | |
dc.contributor.author | Bugianesi, Elisabetta | |
dc.contributor.author | Klein, Samuel | |
dc.contributor.author | Lu, Shelly C. | |
dc.contributor.author | Anstee, Quentin M. | |
dc.contributor.author | Millet Aguilar-Galindo, Oscar | |
dc.contributor.author | Davidson, Nicholas O. | |
dc.contributor.author | Alonso, Cristina | |
dc.contributor.author | Mato, José M. | |
dc.date.accessioned | 2023-02-14T16:41:03Z | |
dc.date.available | 2023-02-14T16:41:03Z | |
dc.date.issued | 2022-10 | |
dc.identifier.citation | Hepatology 76(4) : 1121-1134 (2022) | es_ES |
dc.identifier.issn | 0270-9139 | |
dc.identifier.issn | 1527-3350 | |
dc.identifier.uri | http://hdl.handle.net/10810/59839 | |
dc.description.abstract | Background and Aims We previously identified subsets of patients with NAFLD with different metabolic phenotypes. Here we align metabolomic signatures with cardiovascular disease (CVD) and genetic risk factors. Approach and Results We analyzed serum metabolome from 1154 individuals with biopsy-proven NAFLD, and from four mouse models of NAFLD with impaired VLDL-triglyceride (TG) secretion, and one with normal VLDL-TG secretion. We identified three metabolic subtypes: A (47%), B (27%), and C (26%). Subtype A phenocopied the metabolome of mice with impaired VLDL-TG secretion; subtype C phenocopied the metabolome of mice with normal VLDL-TG; and subtype B showed an intermediate signature. The percent of patients with NASH and fibrosis was comparable among subtypes, although subtypes B and C exhibited higher liver enzymes. Serum VLDL-TG levels and secretion rate were lower among subtype A compared with subtypes B and C. Subtype A VLDL-TG and VLDL-apolipoprotein B concentrations were independent of steatosis, whereas subtypes B and C showed an association with these parameters. Serum TG, cholesterol, VLDL, small dense LDL5,6, and remnant lipoprotein cholesterol were lower among subtype A compared with subtypes B and C. The 10-year high risk of CVD, measured with the Framingham risk score, and the frequency of patatin-like phospholipase domain-containing protein 3 NAFLD risk allele were lower in subtype A. Conclusions Metabolomic signatures identify three NAFLD subgroups, independent of histological disease severity. These signatures align with known CVD and genetic risk factors, with subtype A exhibiting a lower CVD risk profile. This may account for the variation in hepatic versus cardiovascular outcomes, offering clinically relevant risk stratification. | es_ES |
dc.description.sponsorship | National Institutes of Health (R01DK123763, R01DK119437, HL151328, P30DK52574, P30DK56341, and UL1TR002345); Ministerio de Economía y Competitividad de España (SAF2017-88041-R); Ministerio de Economía y Competitividad de España for the Severo Ochoa Excellence Accreditation (SEV-2016-0644); CIBERehd (Biomedical Research Center in Hepatic and Digestive Diseases) and Netherlands Organization for Applied Scientific Research Program (PMC13 and PMC15); Spanish Carlos III Health Institute (PI15/01132 and PI18/01075); Miguel Servet Program (CON14/00129 and CPII19/00008); Fondo Europeo de Desarrollo Regional, CIBERehd, Department of Industry of the Basque Country (Elkartek: KK-2020/00008); La Caixa Scientific Foundation (HR17-00601); Liver Investigation: Testing Marker Utility in Steatohepatitis consortium funded by the Innovative Medicines Initiative Program of the European Union (777377), which receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA; Newcastle NIHR Biomedical Research Center; Czech Ministry of Health (RVO-VFN64165/2020); Fondo Nacional De Ciencia y Tecnología de Chile (1191145); and the Comisión Nacional de Investigación, Ciencia y Tecnología (AFB170005, CARE Chile UC); Agencia Nacional de Investigación y Desarrollo (ANID ACE 210009); European Union's Horizon 2020 Research and Innovation Program (825510). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/777377 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2017-88041-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SEV-2016-0644 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0/es/ | * |
dc.title | Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2022 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. | es_ES |
dc.rights.holder | Atribución-NoComercial 3.0 España | * |
dc.relation.publisherversion | https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.32427 | es_ES |
dc.identifier.doi | 10.1002/hep.32427 | |
dc.contributor.funder | European Commission |
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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.