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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 27, 2024; 16(12): 1468-1479
Published online Dec 27, 2024. doi: 10.4254/wjh.v16.i12.1468
Published online Dec 27, 2024. doi: 10.4254/wjh.v16.i12.1468
Lipophagy and epigenetic alterations are related to metabolic dysfunction-associated steatotic liver disease progression in an experimental model
Felipe Schütz, Larisse Longo, Melina Belén Keingeski, Carolina Uribe-Cruz, Mário Reis Álvares-da-Silva, Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-007, Rio Grande do Sul, Brazil
Felipe Schütz, Larisse Longo, Melina Belén Keingeski, Carolina Uribe-Cruz, Mário Reis Álvares-da-Silva, Experimental Laboratory of Hepatology and Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Rio Grande do Sul, Brazil
Eduardo Filippi-Chiela, Center of Biotechnology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, Rio Grande do Sul, Brazil
Eduardo Filippi-Chiela, Department of Morphological Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, Rio Grande do Sul, Brazil
Carolina Uribe-Cruz, Facultad de Ciencias de la Salud, Universidad Católica de las Misiones, Posadas 3300, Misiones, Argentina
Mário Reis Álvares-da-Silva, Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Rio Grande do Sul, Brazil
Mário Reis Álvares-da-Silva, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brasilia 71.605-001, Distrito Federal, Brazil
Co-first authors: Felipe Schütz and Larisse Longo.
Author contributions: Schütz F, Longo L, Filippi-Chiela E, and Álvares-da-Silva MR performed the conceptualization, methodology, formal analysis, investigation, data curation, writing of the original draft, writing-review, and editing; Keingeski MB and Uribe-Cruz C performed the methodology, formal analysis, and writing-review.
Supported by Financiamento e Incentivo à Pesquisa from Hospital de Clínicas de Porto Alegre, No. 2022-0117 (to Álvares-da-Silva MR); National Council for Scientific and Technological Development, No. CNPq (to Alvares-da-Silva MR); and Coordination for the Improvement of Higher Education Personnel, No. CAPES/PNPD.
Institutional animal care and use committee statement: All experiments and procedures for the use of animals (protocol number: 2022-0117) were approved by the Institutional Ethics Committee. The procedures for the use of scientific animals were conducted in accordance with the Guide for the Care and Use of Laboratory Animals (8th ed, 2011) and law no. 11.794 (Brazil, 2008).
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
Data sharing statement: The results and information will be available upon reasonable request to the corresponding author at
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/.
Corresponding author: Mário Reis Álvares-da-Silva, MD, PhD, Professor, Experimental Laboratory of Hepatology and Gastroenterology, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, n° 2350/Sala 2033, 2° Andar, Porto Alegre 90035-007, Rio Grande do Sul, Brazil. marioreis@live.com
Received: May 7, 2024
Revised: August 31, 2024
Accepted: September 19, 2024
Published online: December 27, 2024
Processing time: 206 Days and 0.4 Hours
Revised: August 31, 2024
Accepted: September 19, 2024
Published online: December 27, 2024
Processing time: 206 Days and 0.4 Hours
Core Tip
Core Tip: The model of metabolic dysfunction-associated steatohepatitis (MASH) can evaluate pathophysiological mechanisms and therapeutic targets for metabolic dysfunction-associated steatotic liver disease (MASLD). Animals with MASH showed increased expression of miR-34a and miR-21, which contribute to the inflammatory process and fibrogenesis of the disease. Additionally, the lipophagy process was reduced due to increased perilipin gene expression and decreased sirtuin-1. Lysosomal stress and autophagic activity increased in MASH through increased expression of transcription factor-EB and decreased levels of p62/sequestosome-1. Alterations in the expression of these genes are related to the inflammatory process and fibrogenesis, which promote the progression of MASLD.