Intestinal Lipid Metabolism Genes Regulated by miRNAs
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 intesti...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2020.00707/full |
| _version_ | 1818848709915443200 |
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| author | María Belén Ruiz-Roso Judit Gil-Zamorano María Carmen López de las Hazas Joao Tomé-Carneiro María Carmen Crespo María Jesús Latasa Olivier Briand Daniel Sánchez-López Ana I. Ortiz Francesco Visioli Francesco Visioli J. Alfredo Martínez J. Alfredo Martínez J. Alfredo Martínez Alberto Dávalos |
| author_facet | María Belén Ruiz-Roso Judit Gil-Zamorano María Carmen López de las Hazas Joao Tomé-Carneiro María Carmen Crespo María Jesús Latasa Olivier Briand Daniel Sánchez-López Ana I. Ortiz Francesco Visioli Francesco Visioli J. Alfredo Martínez J. Alfredo Martínez J. Alfredo Martínez Alberto Dávalos |
| author_sort | María Belén Ruiz-Roso |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T06:21:40Z |
| format | Article |
| id | doaj.art-403a7535d14145189f4aba1464246025 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-19T06:21:40Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-403a7535d14145189f4aba14642460252022-12-21T20:32:41ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-07-011110.3389/fgene.2020.00707544415Intestinal Lipid Metabolism Genes Regulated by miRNAsMaría Belén Ruiz-Roso0Judit Gil-Zamorano1María Carmen López de las Hazas2Joao Tomé-Carneiro3María Carmen Crespo4María Jesús Latasa5Olivier Briand6Daniel Sánchez-López7Ana I. Ortiz8Francesco Visioli9Francesco Visioli10J. Alfredo Martínez11J. Alfredo Martínez12J. Alfredo Martínez13Alberto Dávalos14Laboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, SpainLaboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, SpainLaboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, SpainLaboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, SpainLaboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, SpainResearch Program, Innovation, Communication and Education Program, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, SpainUniversity of Lille, Inserm, Centre Hospitalier Universitaire (CHU) de Lille, Institut Pasteur de Lille, U1011-European Genomic Institute for Diabetes, Lille, FranceUniversity of Lille, Inserm, Centre Hospitalier Universitaire (CHU) de Lille, Institut Pasteur de Lille, U1011-European Genomic Institute for Diabetes, Lille, FranceServicio de Cirugía Experimental, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, SpainLaboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, SpainDepartment of Molecular Medicine, University of Padua, Padua, ItalyDepartment of Nutrition and Physiology, Center for Nutrition Research, University of Navarra, IDISNA Navarra, Pamplona, SpainCentre of Biomedical Research in Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, SpainCardiometabolic Nutrition Group, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, SpainLaboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, SpainMicroRNAs (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.https://www.frontiersin.org/article/10.3389/fgene.2020.00707/fullDicer1lipid metabolismsmall intestinemicroRNAorganoidsHmgcs2 |
| spellingShingle | María Belén Ruiz-Roso Judit Gil-Zamorano María Carmen López de las Hazas Joao Tomé-Carneiro María Carmen Crespo María Jesús Latasa Olivier Briand Daniel Sánchez-López Ana I. Ortiz Francesco Visioli Francesco Visioli J. Alfredo Martínez J. Alfredo Martínez J. Alfredo Martínez Alberto Dávalos Intestinal Lipid Metabolism Genes Regulated by miRNAs Frontiers in Genetics Dicer1 lipid metabolism small intestine microRNA organoids Hmgcs2 |
| title | Intestinal Lipid Metabolism Genes Regulated by miRNAs |
| title_full | Intestinal Lipid Metabolism Genes Regulated by miRNAs |
| title_fullStr | Intestinal Lipid Metabolism Genes Regulated by miRNAs |
| title_full_unstemmed | Intestinal Lipid Metabolism Genes Regulated by miRNAs |
| title_short | Intestinal Lipid Metabolism Genes Regulated by miRNAs |
| title_sort | intestinal lipid metabolism genes regulated by mirnas |
| topic | Dicer1 lipid metabolism small intestine microRNA organoids Hmgcs2 |
| url | https://www.frontiersin.org/article/10.3389/fgene.2020.00707/full |
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