Loss of Cdkn1a protects against MASLD alone or with alcohol intake by preserving lipid homeostasis
Expression of p21, encoded by the <i>CDKN1A</i> gene, has been associated with fibrosis progression in steatotic liver disease (SLD), but the molecular mechanisms remain elusive. Interestingly, in this study we found that <i>Cdkn1a</i> deletion protected against preclinical SLD by promoting fatty acid oxidation and preventing free fatty acid uptake and <i>de novo</i> lipogenesis, via the AMPK-SIRT3 axis. Translationally, <i>Cdkn1a</i> expression was found to be directly correlated with increased severity of NAFLD Activity Score (NAS) and fibrosis in SLD patients, and therefore, CDKN1A might be used potential theragnostic target for the treatment of metabolically induced SLD, with and without alcohol consumption.
Authors
- Matías A. Ávila (ORCID: https://orcid.org/0000-0001-6570-3557)
- Francisco Javier Cubero (ORCID: https://orcid.org/0000-0003-1499-650X)
- Carlos Sanz‐García (ORCID: https://orcid.org/0000-0002-4213-8871)
- Elena Vázquez-Ogando (ORCID: https://orcid.org/0000-0002-5996-5208)
- Jesús Rivera‐Esteban (ORCID: https://orcid.org/0000-0003-4357-8817)
- Beste Mutlu (ORCID: https://orcid.org/0000-0003-3258-0452)
- Arantza Lamas‐Paz (ORCID: https://orcid.org/0000-0001-5857-4320)
- Yulia Alexandrowna Nevzorova (ORCID: https://orcid.org/0000-0003-1390-8002)
- David Sanfeliu-Redondo (ORCID: https://orcid.org/0000-0002-5617-0637)
- Pilar Iniesta (ORCID: https://orcid.org/0000-0002-1259-9810)
- Isabel Graupera (ORCID: https://orcid.org/0000-0001-9170-9784)
- Bruno Ramos‐Molina (ORCID: https://orcid.org/0000-0001-6804-5449)
- Manuel Romero‐Gómez (ORCID: https://orcid.org/0000-0001-8494-8947)
- Jordi Gracia‐Sancho (ORCID: https://orcid.org/0000-0001-7736-4089)
- Javier Ampuero (ORCID: https://orcid.org/0000-0002-8332-2122)
- María Isabel Peligros
- Olga Estévez‐Vázquez (ORCID: https://orcid.org/0000-0002-7983-8521)
- Kang Zheng (ORCID: https://orcid.org/0000-0001-6778-2607)
- Juan M. Pericàs (ORCID: https://orcid.org/0000-0002-3645-3293)
- Eduardo Martı́nez-Naves (ORCID: https://orcid.org/0000-0001-8136-9042)
- Beatriz Gómez‐Santos (ORCID: https://orcid.org/0000-0001-6607-7973)
- Mariana Mesquita (ORCID: https://orcid.org/0000-0003-4022-6736)
- Iris Asensio
- Mar Coll (ORCID: https://orcid.org/0000-0003-3726-0087)
- Pere Puigserver (ORCID: https://orcid.org/0000-0002-0884-2718)
- Douglas Maya‐Miles
- Pere Ginès (ORCID: https://orcid.org/0000-0003-4657-4504)
- María Dolores Frutos (ORCID: https://orcid.org/0000-0002-2111-4715)
- Patricia Aspichueta (ORCID: https://orcid.org/0000-0002-3553-1755)
- Maria Luz Martínez‐Chantar (ORCID: https://orcid.org/0000-0002-6446-9911)
- Teresa C. Delgado (ORCID: https://orcid.org/0000-0001-9204-581X)
- Ana Martínez-Alcocer (ORCID: https://orcid.org/0000-0003-2941-8198)
- Marina S. Mazariegos (ORCID: https://orcid.org/0000-0002-3298-9461)
- Carlos Martínez (ORCID: https://orcid.org/0000-0003-3307-1326)
- Andreea Ciudin (ORCID: https://orcid.org/0000-0001-5622-0203)
- Sofía Tesolato (ORCID: https://orcid.org/0009-0004-8495-3972)
- Alejandro Hionides-Gutiérrez
- Laura Morán-Blanco
- Mohamed Ramadan Mohamed (ORCID: https://orcid.org/0000-0002-2101-2030)
- Feifei Guo (ORCID: https://orcid.org/0000-0002-5422-8209)
- Javier Vaquero (ORCID: https://orcid.org/0000-0001-8903-7288)
- Rocío Gallego-Durán
- Elena Blázquez‐López
- Rafael Bañares
- Raquel Benedé-Ubieto
- Gonzalo Jorquera
- Anabel Fernández-Iglesias
Institutions
- University of Bern (CH)
- Universidad Complutense de Madrid (ES)
- Nanjing University of Chinese Medicine (CN)
- Harvard University (US)
- University of the Basque Country (ES)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- University Hospital of Bern (CH)
- Hospital General Universitario Gregorio Marañón (ES)
- Research Institute Hospital 12 de Octubre (ES)
- BioCruces Health research Institute (ES)
- Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (ES)
- Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (ES)
- Vall d'Hebron Institut de Recerca (ES)
- Hospital Universitario Puerta de Hierro Majadahonda (ES)
- Nanjing Drum Tower Hospital (CN)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Navarre Institute of Health Research (ES)
- CIC bioGUNE (ES)
- Hospital Clínic de Barcelona (ES)
- Dana-Farber Cancer Institute (US)
- Institut d'Investigacions Biomèdiques de Barcelona (ES)
- Instituto de Biomedicina de Sevilla (ES)
- Instituto Murciano de Investigación Biosanitaria (ES)
- Hospital Universitario Virgen de la Arrixaca (ES)
- Hospital Universitario Virgen del Rocío (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Medical Research Network (US)
- University of Chile (CL)
- Universidad de Sevilla (ES)
- University of Valparaíso (CL)
- Universidad de Navarra (ES)
- RWTH Aachen University (DE)
Publication Details
- Journal
- JHEP Reports
- Published
- 2024-10-05
- DOI
- https://doi.org/10.1016/j.jhepr.2024.101230
- Citations
- 8
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 4.58
Funders
- U.S. Department of Education
- Comunidad de Madrid
- Real Colegio Complutense
- Ministerio de Ciencia, Innovación y Universidades
- Eusko Jaurlaritza
- Instituto de Salud Carlos III
- European Regional Development Fund
- Agencia Estatal de Investigación
- HORIZON EUROPE Health