在一个实验模型中，脂质自噬和表观遗传改变与代谢功能障碍相关脂肪性肝病进展有关。

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

作者信息

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

机构信息

Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-007, Rio Grande do Sul, Brazil.

Experimental Laboratory of Hepatology and Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Rio Grande do Sul, Brazil.

出版信息

World J Hepatol. 2024 Dec 27;16(12):1468-1479. doi: 10.4254/wjh.v16.i12.1468.

DOI:10.4254/wjh.v16.i12.1468

PMID:39744199

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11686535/

Abstract

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 ( = 10) fed a standard diet; and intervention group ( = 10) fed a high-fat-choline-deficient diet for 16 weeks. Molecular evaluation of lipophagy markers in liver tissue [sirtuin-1, p62/sequestosome-1, transcription factor-EB, perilipin-2 , , , lysosome-associated membrane proteins-2, rubicon, and ], and serum miRNAs were performed.

RESULTS

Animals in the intervention group developed MASH and showed a significant decrease in sirtuin-1 ( = 0.020) and p62/sequestosome-1 ( < 0.001); the opposite was reported for transcription factor-EB ( = 0.020), ( = 0.003), ( = 0.031), and ( = 0.005) compared to the control group. There was no significant difference between groups for lysosome-associated membrane proteins-2 ( = 0.715), rubicon ( = 0.166), and ( = 0.312). The intervention group showed a significant increase in miR-34a ( = 0.005) and miR-21 ( = 0.043) compared to the control. There was no significant difference between groups for miR-375 ( = 0.905), miR-26b ( = 0.698), and miR-155 ( = 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.

摘要

背景

基因和表观遗传改变与代谢功能障碍相关脂肪性肝病（MASLD）的发病机制有关。

目的

评估代谢功能障碍相关脂肪性肝炎（MASH）实验模型中的微小（mi）RNA和脂噬标志物。

方法

将成年雄性Sprague Dawley大鼠随机分为两组：对照组（n = 10）给予标准饮食；干预组（n = 10）给予高脂低胆碱饮食16周。对肝组织中的脂噬标志物[沉默调节蛋白-1、p62/聚集体蛋白-1、转录因子-EB、脂滴包被蛋白-2、、、溶酶体相关膜蛋白-2、含RUN结构域和半胱氨酸蛋白酶激活结构域的蛋白、 ]以及血清miRNA进行分子评估。

结果

干预组动物发生了MASH，沉默调节蛋白-1（P = 0.020）和p62/聚集体蛋白-1（P < 0.001）显著降低；与对照组相比，转录因子-EB（P = 0.020）、（P = 0.003）、（P = 0.031）和（P = 0.005）则相反。溶酶体相关膜蛋白-2（P = 0.715）、含RUN结构域和半胱氨酸蛋白酶激活结构域的蛋白（P = 0.166）和（P = 0.312）在两组之间无显著差异。与对照组相比，干预组的miR-34a（P = 0.005）和miR-21（P = 0.043）显著增加。miR-375（P = 0.905）、miR-26b（P = 0.698）和miR-155（P = 0.688）在两组之间无显著差异。