Lipophagy and epigenetic alterations are related to metabolic dysfunction-associated steatotic liver disease progression in an experimental model  

作　　者：Felipe Schütz Larisse Longo Melina Belén Keingeski Eduardo Filippi-Chiela Carolina Uribe-Cruz Mário Reis Álvares-da-Silva 

机构地区：[1]Graduate Program in Gastroenterology and Hepatology,Universidade Federal do Rio Grande do Sul,Porto Alegre 90035-007,Rio Grande do Sul,Brazil [2]Experimental Laboratory of Hepatology and Gastroenterology,Hospital de Clínicas de Porto Alegre,Porto Alegre 90035-007,Rio Grande do Sul,Brazil [3]Center of Biotechnology,Universidade Federal do Rio Grande do Sul,Porto Alegre 90035-003,Rio Grande do Sul,Brazil [4]Department of Morphological Sciences,Universidade Federal do Rio Grande do Sul,Porto Alegre 90035-003,Rio Grande do Sul,Brazil [5]Facultad de Ciencias de la Salud,Universidad Católica de las Misiones,Posadas 3300,Misiones,Argentina [6]Division of Gastroenterology,Hospital de Clínicas de Porto Alegre,Porto Alegre 90035-007,Rio Grande do Sul,Brazil [7]Conselho Nacional de Desenvolvimento Científico e Tecnológico,Brasilia 71.605-001,Distrito Federal,Brazil

出　　处：《World Journal of Hepatology》2024年第12期1468-1479,共12页世界肝病学杂志（英文）

基　　金：Supported by Financiamento e IncentivoàPesquisa from Hospital de Clínicas de Porto Alegre,No.2022-0117(toÁlvares-da-Silva MR);National Council for Scientific and Technological Development,No.CNPq(to Alvares-da-Silva MR);Coordination for the Improvement of Higher Education Personnel,No.CAPES/PNPD.

摘　　要：BACKGROUND Genetic and epigenetic alterations are related to metabolic dysfunction-associated steatotic liver disease(MASLD)pathogenesis.AIM To evaluate micro(mi)RNAs and lipophagy markers in an experimental model of metabolic dysfunction-associated steatohepatitis(MASH).METHODS Adult male Sprague Dawley rats were randomized into two groups:Control group(n=10)fed a standard diet;and intervention group(n=10)fed a high-fat-choline-deficient diet for 16 weeks.Molecular evaluation of li-pophagy markers in liver tissue[sirtuin-1,p62/sequestosome-1,transcription factor-EB,perilipin-2(Plin2),Plin3,Plin5,lysosome-associated membrane proteins-2,rubicon,and Cd36],and serum miRNAs were performed.RESULTS Animals in the intervention group developed MASH and showed a significant decrease in sirtuin-1(P=0.020)and p62/sequestosome-1(P<0.001);the opposite was reported for transcription factor-EB(P=0.020),Plin2(P=0.003),Plin3(P=0.031),and Plin5(P=0.005)compared to the control group.There was no significant difference between groups for lysosome-associated membrane proteins-2(P=0.715),rubicon(P=0.166),and Cd36(P=0.312).The intervention group showed a significant increase in miR-34a(P=0.005)and miR-21(P=0.043)compared to the control.There was no significant difference between groups for miR-375(P=0.905),miR-26b(P=0.698),and miR-155(P=0.688).CONCLUSION Animals with MASH presented expression changes in markers related to lysosomal stress and autophagy as well as in miRNAs related to inflammation and fibrogenesis,processes that promote MASLD progression.

关 键 词：Animal model EPIGENETIC Lipophagy MicroRNAs Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis 

分 类 号：R657.3[医药卫生—外科学] R575.5[医药卫生—临床医学]