Intestinal Lipid Metabolism Genes Regulated by miRNAs

Frontiers in Genetics

卷:11

J. Alfredo Martínez¹  Francesco Visioli³  Judit Gil-Zamorano⁵  María Carmen López de las Hazas⁵  María Belén Ruiz-Roso⁵  Alberto Dávalos⁵  María Carmen Crespo⁶  Joao Tomé-Carneiro⁶  María Jesús Latasa⁷  Ana I. Ortiz⁸  Olivier Briand⁹  Daniel Sánchez-López⁹ 

[1] Cardiometabolic Nutrition Group, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, Spain;

[2] Centre of Biomedical Research in Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain;

[3] Department of Molecular Medicine, University of Padua, Padua, Italy;

[4] Department of Nutrition and Physiology, Center for Nutrition Research, University of Navarra, IDISNA Navarra, Pamplona, Spain;

[5] Laboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, Spain;

[6] Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, Spain;

[7] Research Program, Innovation, Communication and Education Program, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, Spain;

[8] Servicio de Cirugía Experimental, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain;

[9] University of Lille, Inserm, Centre Hospitalier Universitaire (CHU) de Lille, Institut Pasteur de Lille, U1011-European Genomic Institute for Diabetes, Lille, France;

关键词: Dicer1;    lipid metabolism;    small intestine;    microRNA;    organoids;    Hmgcs2;   

DOI  :  10.3389/fgene.2020.00707

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown