Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4
Abstract Background and aims The hallmark of non-alcoholic fatty liver disease (NAFLD) is the excessive hepatic lipid accumulation. Currently, no pharmacotherapy exists for NAFLD. However, the glucagon-like peptide-1 receptor agonists have recently emerged as potential therapeutics. Here, we sought...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-021-02885-4 |
| _version_ | 1830307933756325888 |
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| author | Khaoula Errafii Neyla S. Al-Akl Olfa Khalifa Abdelilah Arredouani |
| author_facet | Khaoula Errafii Neyla S. Al-Akl Olfa Khalifa Abdelilah Arredouani |
| author_sort | Khaoula Errafii |
| collection | DOAJ |
| description | Abstract Background and aims The hallmark of non-alcoholic fatty liver disease (NAFLD) is the excessive hepatic lipid accumulation. Currently, no pharmacotherapy exists for NAFLD. However, the glucagon-like peptide-1 receptor agonists have recently emerged as potential therapeutics. Here, we sought to identify the long non-coding RNAs (LncRNAs) associated with the steatosis improvement induced by the GLP-1R agonist Exendin-4 (Ex-4) in vitro. Methods Steatosis was induced in HepG2 cells with oleic acid. The transcriptomic profiling was performed using total RNA extracted from untreated, steatotic, and Ex-4-treated steatotic cells. We validated a subset of differentially expressed LncRNAs with qRT-PCR and identified the most significantly enriched cellular functions associated with the relevant LncRNAs. Results We confirm that Ex-4 improves steatosis in HepG2 cells. We found 379 and 180 differentially expressed LncRNAs between untreated and steatotic cells and between steatotic and Ex-4-treated steatotic cells, respectively. Interestingly, 22 upregulated LncRNAs in steatotic cells became downregulated with Ex-4 exposure, while 50 downregulated LncRNAs in steatotic cells became upregulated in the presence of Ex-4. Although some LncRNAs, such as MALAT1, H19, and NEAT1, were previously associated with NAFLD, the association of others with steatosis and the positive effect of Ex-4 is being reported for the first time. Functional enrichment analysis identified many critical pathways, including fatty acid and pyruvate metabolism, and insulin, PPAR, Wnt, TGF-β, mTOR, VEGF, NOD-like, and Toll-like receptors signaling pathways. Conclusion Our results suggest that LncRNAs may play essential roles in the mechanisms underlying steatosis improvement in response to GLP-1R agonists and warrant further functional studies. |
| first_indexed | 2024-12-19T10:41:22Z |
| format | Article |
| id | doaj.art-27d947c8f2114284985e57f923e3d031 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-19T10:41:22Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-27d947c8f2114284985e57f923e3d0312022-12-21T20:25:27ZengBMCJournal of Translational Medicine1479-58762021-06-0119111110.1186/s12967-021-02885-4Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4Khaoula Errafii0Neyla S. Al-Akl1Olfa Khalifa2Abdelilah Arredouani3College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar FoundationDiabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar FoundationDiabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar FoundationCollege of Health and Life Sciences, Hamad Bin Khalifa University, Qatar FoundationAbstract Background and aims The hallmark of non-alcoholic fatty liver disease (NAFLD) is the excessive hepatic lipid accumulation. Currently, no pharmacotherapy exists for NAFLD. However, the glucagon-like peptide-1 receptor agonists have recently emerged as potential therapeutics. Here, we sought to identify the long non-coding RNAs (LncRNAs) associated with the steatosis improvement induced by the GLP-1R agonist Exendin-4 (Ex-4) in vitro. Methods Steatosis was induced in HepG2 cells with oleic acid. The transcriptomic profiling was performed using total RNA extracted from untreated, steatotic, and Ex-4-treated steatotic cells. We validated a subset of differentially expressed LncRNAs with qRT-PCR and identified the most significantly enriched cellular functions associated with the relevant LncRNAs. Results We confirm that Ex-4 improves steatosis in HepG2 cells. We found 379 and 180 differentially expressed LncRNAs between untreated and steatotic cells and between steatotic and Ex-4-treated steatotic cells, respectively. Interestingly, 22 upregulated LncRNAs in steatotic cells became downregulated with Ex-4 exposure, while 50 downregulated LncRNAs in steatotic cells became upregulated in the presence of Ex-4. Although some LncRNAs, such as MALAT1, H19, and NEAT1, were previously associated with NAFLD, the association of others with steatosis and the positive effect of Ex-4 is being reported for the first time. Functional enrichment analysis identified many critical pathways, including fatty acid and pyruvate metabolism, and insulin, PPAR, Wnt, TGF-β, mTOR, VEGF, NOD-like, and Toll-like receptors signaling pathways. Conclusion Our results suggest that LncRNAs may play essential roles in the mechanisms underlying steatosis improvement in response to GLP-1R agonists and warrant further functional studies.https://doi.org/10.1186/s12967-021-02885-4SteatosisNAFLDExendin-4LncRNAsHepG2GLP-1R agonist |
| spellingShingle | Khaoula Errafii Neyla S. Al-Akl Olfa Khalifa Abdelilah Arredouani Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4 Journal of Translational Medicine Steatosis NAFLD Exendin-4 LncRNAs HepG2 GLP-1R agonist |
| title | Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4 |
| title_full | Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4 |
| title_fullStr | Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4 |
| title_full_unstemmed | Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4 |
| title_short | Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4 |
| title_sort | comprehensive analysis of lncrnas expression profiles in an in vitro model of steatosis treated with exendin 4 |
| topic | Steatosis NAFLD Exendin-4 LncRNAs HepG2 GLP-1R agonist |
| url | https://doi.org/10.1186/s12967-021-02885-4 |
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