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Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles
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‐prov...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9790568/ https://www.ncbi.nlm.nih.gov/pubmed/35220605 http://dx.doi.org/10.1002/hep.32427 |
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author | Martínez‐Arranz, Ibon Bruzzone, Chiara Noureddin, Mazen Gil‐Redondo, Ruben Mincholé, Itziar Bizkarguenaga, Maider Arretxe, Enara Iruarrizaga‐Lejarreta, Marta Fernández‐Ramos, David Lopitz‐Otsoa, Fernando Mayo, Rebeca Embade, Nieves Newberry, Elizabeth Mittendorf, Bettina Izquierdo‐Sánchez, Laura Smid, Vaclav Arnold, Jorge Iruzubieta, Paula Pérez Castaño, Ylenia Krawczyk, Marcin Marigorta, Urko M. Morrison, Martine C. Kleemann, Robert Martín‐Duce, Antonio Hayardeny, Liat Vitek, Libor Bruha, Radan Aller de la Fuente, Rocío Crespo, Javier Romero‐Gomez, Manuel Banales, Jesus M Arrese, Marco Cusi, Kenneth Bugianesi, Elisabetta Klein, Samuel Lu, Shelly C. Anstee, Quentin M. Millet, Oscar Davidson, Nicholas O. Alonso, Cristina Mato, José M. |
author_facet | Martínez‐Arranz, Ibon Bruzzone, Chiara Noureddin, Mazen Gil‐Redondo, Ruben Mincholé, Itziar Bizkarguenaga, Maider Arretxe, Enara Iruarrizaga‐Lejarreta, Marta Fernández‐Ramos, David Lopitz‐Otsoa, Fernando Mayo, Rebeca Embade, Nieves Newberry, Elizabeth Mittendorf, Bettina Izquierdo‐Sánchez, Laura Smid, Vaclav Arnold, Jorge Iruzubieta, Paula Pérez Castaño, Ylenia Krawczyk, Marcin Marigorta, Urko M. Morrison, Martine C. Kleemann, Robert Martín‐Duce, Antonio Hayardeny, Liat Vitek, Libor Bruha, Radan Aller de la Fuente, Rocío Crespo, Javier Romero‐Gomez, Manuel Banales, Jesus M Arrese, Marco Cusi, Kenneth Bugianesi, Elisabetta Klein, Samuel Lu, Shelly C. Anstee, Quentin M. Millet, Oscar Davidson, Nicholas O. Alonso, Cristina Mato, José M. |
author_sort | Martínez‐Arranz, Ibon |
collection | PubMed |
description | 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 LDL(5,6), 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. |
format | Online Article Text |
id | pubmed-9790568 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97905682022-12-28 Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles Martínez‐Arranz, Ibon Bruzzone, Chiara Noureddin, Mazen Gil‐Redondo, Ruben Mincholé, Itziar Bizkarguenaga, Maider Arretxe, Enara Iruarrizaga‐Lejarreta, Marta Fernández‐Ramos, David Lopitz‐Otsoa, Fernando Mayo, Rebeca Embade, Nieves Newberry, Elizabeth Mittendorf, Bettina Izquierdo‐Sánchez, Laura Smid, Vaclav Arnold, Jorge Iruzubieta, Paula Pérez Castaño, Ylenia Krawczyk, Marcin Marigorta, Urko M. Morrison, Martine C. Kleemann, Robert Martín‐Duce, Antonio Hayardeny, Liat Vitek, Libor Bruha, Radan Aller de la Fuente, Rocío Crespo, Javier Romero‐Gomez, Manuel Banales, Jesus M Arrese, Marco Cusi, Kenneth Bugianesi, Elisabetta Klein, Samuel Lu, Shelly C. Anstee, Quentin M. Millet, Oscar Davidson, Nicholas O. Alonso, Cristina Mato, José M. Hepatology Original Articles 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 LDL(5,6), 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. John Wiley and Sons Inc. 2022-03-17 2022-10 /pmc/articles/PMC9790568/ /pubmed/35220605 http://dx.doi.org/10.1002/hep.32427 Text en © 2022 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Martínez‐Arranz, Ibon Bruzzone, Chiara Noureddin, Mazen Gil‐Redondo, Ruben Mincholé, Itziar Bizkarguenaga, Maider Arretxe, Enara Iruarrizaga‐Lejarreta, Marta Fernández‐Ramos, David Lopitz‐Otsoa, Fernando Mayo, Rebeca Embade, Nieves Newberry, Elizabeth Mittendorf, Bettina Izquierdo‐Sánchez, Laura Smid, Vaclav Arnold, Jorge Iruzubieta, Paula Pérez Castaño, Ylenia Krawczyk, Marcin Marigorta, Urko M. Morrison, Martine C. Kleemann, Robert Martín‐Duce, Antonio Hayardeny, Liat Vitek, Libor Bruha, Radan Aller de la Fuente, Rocío Crespo, Javier Romero‐Gomez, Manuel Banales, Jesus M Arrese, Marco Cusi, Kenneth Bugianesi, Elisabetta Klein, Samuel Lu, Shelly C. Anstee, Quentin M. Millet, Oscar Davidson, Nicholas O. Alonso, Cristina Mato, José M. Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles |
title | Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles |
title_full | Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles |
title_fullStr | Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles |
title_full_unstemmed | Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles |
title_short | Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles |
title_sort | metabolic subtypes of patients with nafld exhibit distinctive cardiovascular risk profiles |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9790568/ https://www.ncbi.nlm.nih.gov/pubmed/35220605 http://dx.doi.org/10.1002/hep.32427 |
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