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

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World Journal of Hepatology 2024年第12期16卷 1468-1479页

作者： Felipe Schütz Larisse Longo melina belén keingeski Eduardo Filippi-Chiela Carolina Uribe-Cruz Mário ReisÁlvares-da-Silva Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-007Rio Grande do SulBrazil Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Rio Grande do SulBrazil Center of Biotechnology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Department of Morphological Sciences Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadas 3300MisionesArgentina Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Rio Grande do SulBrazil Conselho nacional de Desenvolvimento Científico e Tecnológico Brasilia 71.605-001Distrito FederalBrazil

BACKGROUnD Genetic and epigenetic alterations are related to metabolic dysfunction-associated steatotic liver disease(MASLD)*** 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 *** 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 *** Animals in the intervention group developed MASH and showed a significant decrease in sirtuin-1(P=0.020)and p62/sequestosome-1(Pnscription factor-EB(P=0.020),Plin2(P=0.003),Plin3(P=0.031),and Plin5(P=0.005)compared to the control *** 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 *** 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

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Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

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World Journal of Hepatology 2024年第1期16卷 75-90页

作者： Matheus Truccolo Michalczuk Larisse Longo melina belén keingeski Bruno de Souza Basso Gabriel Tayguara Silveira Guerreiro Jessica T Ferrari JoséEduardo Vargas Cláudia P Oliveira Carolina Uribe-Cruz Carlos Thadeu Schmidt Cerski Eduardo Filippi-Chiela Mário ReisÁlvares-da-Silva Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Laboratory of Inflammatory and neoplastic Cells Universidade Federal do ParanáParaná81530900Brazil Department of Gastroenterology(LIM07) Faculdade de Medicina da Universidade de São PauloSão Paulo 01246903Brazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadasMisiones 3300Argentina Unit of Surgical Pathology Hospital de Clinicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Center of Biotechnology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Department of Morphological Sciences Universidade Federal do Rio Grande do SulPorto Alegre 90.050-170Rio Grande do SulBrazil Conselho nacional de Desenvolvimento Científico e Tecnológico(CnPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)ResearcherBrasília 71.605-001Brazil

BACKGROUnD Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in *** Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEn)in drinking water and Veh gavage],and RIF[HFCD,DEn and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRnAs were *** All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop *** animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the *** opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-*** with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(Pn HCC compared to RIF(Pn of Mmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(Pn of p62/SQSTM1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and Mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(Pn HCC compared to RIF,and the inverse was observed for miR-224(Pno difference among groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).COnCLUSIOn RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis throu

关键词： Animal model Autophagy Epigenetic Hepatocellular carcinoma Metabolic dysfunction-associated steatotic liver disease Rifaximin

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