RT Journal Article
T1 RNA expression changes driven by altered epigenetics status related to NASH etiology
A1 Castellano Castillo, Daniel
A1 Ramos-Molina, Bruno
A1 Frutos, María Dolores
A1 Arranz-Salas, Isabel María
A1 Reyes-Engel, Armando
A1 Queipo-Ortuño, María Isabel
A1 Cardona-Díaz, Fernando
K1 Obesidad
K1 Hígado - Etiología
AB Non-alcoholic fatty liver disease (NAFLD) is a growing health problem due to the increased obesity rates, amongother factors. In its more severe stage (NASH), inflammation, hepatocellular ballooning and fibrosis are presentin the liver, which can further evolve to total liver dysfunction or even hepatocarcinoma. As a metabolic disease,is associated to environmental factors such as diet and lifestyle conditions, which in turn can influence theepigenetic landscape of the cells, affecting to the gene expression profile and chromatin organization. In thisstudy we performed ATAC-sequencing and RNA-sequencing to interrogate the chromatin status of liver biopsiesin subjects with and without NASH and its effects on RNA transcription and NASH etiology. NASH subjectsshowed transcriptional downregulation for lipid and glucose metabolic pathways (e.g., ABC transporters, AMPK,FoxO or insulin pathways). A total of 229 genes were differentially enriched (ATAC and mRNA) in NASH, whichwere mainly related to lipid transport activity, nuclear receptor-binding, dicarboxylic acid transporter, andPPARA lipid regulation. Interpolation of ATAC data with known liver enhancer regions showed differentialopenness at 8 enhancers, some linked to genes involved in lipid metabolism, (i.e., FASN) and glucose homeostasis(i.e., GCGR). In conclusion, the chromatin landscape is altered in NASH patients compared to patients withoutthis liver condition. This alteration might cause mRNA changes explaining, at least partially, the etiology andpathophysiology of the disease.
PB ELSEVIER
YR 2024
FD 2024-04
LK https://hdl.handle.net/10630/31026
UL https://hdl.handle.net/10630/31026
LA eng
NO Daniel Castellano-Castillo, Bruno Ramos-Molina, María Dolores Frutos, Isabel Arranz-Salas, Armando Reyes-Engel, María Isabel Queipo-Ortuño, Fernando Cardona, RNA expression changes driven by altered epigenetics status related to NASH etiology, Biomedicine & Pharmacotherapy, Volume 174, 2024, 116508, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2024.116508.
NO Partial funding for open access charge: Universidad de Málaga / CBUA
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026