RT Journal Article T1 Intestinal Lipid Metabolism Genes Regulated by miRNAs A1 Ruiz Roso, María Belén A1 Dávalos, Alberto AB MicroRNAs (miRNAs) crucial roles in translation repression and post-transcriptional adjustments contribute to regulate intestinal lipid metabolism. Even though their actions in different metabolic tissues have been elucidated, their intestinal activity is yet unclear. We aimed to investigate intestinal miRNA-regulated lipid metabolism-related genes, by creating an intestinal-specific Dicer1 knockout (Int-Dicer1 KO) mouse model, with a depletion of microRNAs in enterocytes. The levels of 83 cholesterol and lipoprotein metabolism-related genes were assessed in the intestinal mucosa of Int-Dicer1 KO and Wild Type C57BL/6 (WT) littermates mice at baseline and 2 h after an oral lipid challenge. Among the 18 genes selected for further validation, Hmgcs2, Acat1 and Olr1 were found to be strong candidates to be modulated by miRNAs in enterocytes and intestinal organoids. Moreover, we report that intestinal miRNAs contribute to the regulation of intestinal epithelial differentiation. Twenty-nine common miRNAs found in the intestines were analyzed for their potential to target any of the three candidate genes found and validated by miRNA-transfection assays in Caco-2 cells. MiR-31-5p, miR-99b-5p, miR-200a-5p, miR-200b-5p and miR-425-5p are major regulators of these lipid metabolism-related genes. Our data provide new evidence on the potential of intestinal miRNAs as therapeutic targets in lipid metabolism-associated pathologies. PB Frontiers Media SN 1664-8021 YR 2020 FD 2020-07 LK https://hdl.handle.net/20.500.14352/132139 UL https://hdl.handle.net/20.500.14352/132139 LA eng NO Ruiz-Roso MB, Gil-Zamorano J, López de Las Hazas MC, Tomé-Carneiro J, Crespo MC, Latasa MJ, Briand O, Sánchez-López D, Ortiz AI, Visioli F, Martínez JA, Dávalos A. Intestinal Lipid Metabolism Genes Regulated by miRNAs. Front Genet. 2020 Jul 10;11:707. doi: 10.3389/fgene.2020.00707. PMID: 32742270; PMCID: PMC7366872. DS Docta Complutense RD 28 mar 2026