Comparative Transcriptome Analysis Reveals That Exendin-4 Improves Steatosis in HepG2 Cells by Modulating Signaling Pathways Related to Lipid Metabolism
<p dir="ltr">No therapy exists for non-alcoholic fatty liver disease (NAFLD). However, glucagon-like peptide receptor agonists (GLP-1RAs) showed a beneficial effect on NAFLD, although the underpinning mechanisms remain unclear due to their pleiotropic effects. We examined the implica...
محفوظ في:
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| مؤلفون آخرون: | , , |
| منشور في: |
2022
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| _version_ | 1864513519131557888 |
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| author | Khaoula Errafii (10914446) |
| author2 | Olfa Khalifa (10914452) Neyla S. Al-Akl (10914449) Abdelilah Arredouani (10914455) |
| author2_role | author author author |
| author_facet | Khaoula Errafii (10914446) Olfa Khalifa (10914452) Neyla S. Al-Akl (10914449) Abdelilah Arredouani (10914455) |
| author_role | author |
| dc.creator.none.fl_str_mv | Khaoula Errafii (10914446) Olfa Khalifa (10914452) Neyla S. Al-Akl (10914449) Abdelilah Arredouani (10914455) |
| dc.date.none.fl_str_mv | 2022-04-28T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/biomedicines10051020 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Comparative_Transcriptome_Analysis_Reveals_That_Exendin-4_Improves_Steatosis_in_HepG2_Cells_by_Modulating_Signaling_Pathways_Related_to_Lipid_Metabolism/25624290 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Genetics steatosis GLP-1R agonist NAFLD HepG2 Exendin-4 |
| dc.title.none.fl_str_mv | Comparative Transcriptome Analysis Reveals That Exendin-4 Improves Steatosis in HepG2 Cells by Modulating Signaling Pathways Related to Lipid Metabolism |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">No therapy exists for non-alcoholic fatty liver disease (NAFLD). However, glucagon-like peptide receptor agonists (GLP-1RAs) showed a beneficial effect on NAFLD, although the underpinning mechanisms remain unclear due to their pleiotropic effects. We examined the implicated signaling pathways using comparative transcriptomics in a cell model of steatosis to overcome pleiotropy. We treated steatotic HepG2 cells with the GLP-1RA Exendin-4 (Ex-4). We compared the transcriptome profiles of untreated steatotic, and Ex-4-treated steatotic cells, and used Ingenuity Pathway Analysis (IPA) to identify the signaling pathways and associated genes involved in the protective effect of Ex-4. Ex-4 treatment significantly reduces steatosis. RNA-seq analysis revealed 209 differentially expressed genes (DEGs) between steatotic and untreated cells, with farnesoid X receptor/retinoid X receptor (FXR/RXR) (p = 8.9 × 10<sup>−7</sup>) activation being the top regulated canonical pathway identified by IPA. Furthermore, 1644 DEGs were identified between steatotic cells and Ex-4-treated cells, with liver X receptor/retinoid X receptor (LXR/RXR) (p = 2.02 × 10<sup>−7</sup>) and FXR/RXR (p = 3.28 × 10<sup>−7</sup>) activation being the two top canonical pathways. The top molecular and cellular functions between untreated and steatotic cells were lipid metabolism, molecular transport, and small molecular biochemistry, while organismal injury and abnormalities, endocrine system disorders, and gastrointestinal disease were the top three molecular and cellular functions between Ex-4-treated and steatotic cells. Genes overlapping steatotic cells and Ex-4-treated cells were associated with several lipid metabolism processes. Unique transcriptomic differences exist between steatotic cells and Ex-4-treated steatotic cells, providing an important resource for understanding the mechanisms that underpin the protective effect of GLP-1RAs on NAFLD and for the identification of novel therapeutic targets for NAFLD.</p><p><br></p><h2>Other Information</h2><p dir="ltr">Published in: Biomedicines<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/biomedicines10051020" target="_blank">https://dx.doi.org/10.3390/biomedicines10051020</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_3bffd0b960256db31cba0af02f5e18d0 |
| identifier_str_mv | 10.3390/biomedicines10051020 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25624290 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Comparative Transcriptome Analysis Reveals That Exendin-4 Improves Steatosis in HepG2 Cells by Modulating Signaling Pathways Related to Lipid MetabolismKhaoula Errafii (10914446)Olfa Khalifa (10914452)Neyla S. Al-Akl (10914449)Abdelilah Arredouani (10914455)Biological sciencesBiochemistry and cell biologyGeneticssteatosisGLP-1R agonistNAFLDHepG2Exendin-4<p dir="ltr">No therapy exists for non-alcoholic fatty liver disease (NAFLD). However, glucagon-like peptide receptor agonists (GLP-1RAs) showed a beneficial effect on NAFLD, although the underpinning mechanisms remain unclear due to their pleiotropic effects. We examined the implicated signaling pathways using comparative transcriptomics in a cell model of steatosis to overcome pleiotropy. We treated steatotic HepG2 cells with the GLP-1RA Exendin-4 (Ex-4). We compared the transcriptome profiles of untreated steatotic, and Ex-4-treated steatotic cells, and used Ingenuity Pathway Analysis (IPA) to identify the signaling pathways and associated genes involved in the protective effect of Ex-4. Ex-4 treatment significantly reduces steatosis. RNA-seq analysis revealed 209 differentially expressed genes (DEGs) between steatotic and untreated cells, with farnesoid X receptor/retinoid X receptor (FXR/RXR) (p = 8.9 × 10<sup>−7</sup>) activation being the top regulated canonical pathway identified by IPA. Furthermore, 1644 DEGs were identified between steatotic cells and Ex-4-treated cells, with liver X receptor/retinoid X receptor (LXR/RXR) (p = 2.02 × 10<sup>−7</sup>) and FXR/RXR (p = 3.28 × 10<sup>−7</sup>) activation being the two top canonical pathways. The top molecular and cellular functions between untreated and steatotic cells were lipid metabolism, molecular transport, and small molecular biochemistry, while organismal injury and abnormalities, endocrine system disorders, and gastrointestinal disease were the top three molecular and cellular functions between Ex-4-treated and steatotic cells. Genes overlapping steatotic cells and Ex-4-treated cells were associated with several lipid metabolism processes. Unique transcriptomic differences exist between steatotic cells and Ex-4-treated steatotic cells, providing an important resource for understanding the mechanisms that underpin the protective effect of GLP-1RAs on NAFLD and for the identification of novel therapeutic targets for NAFLD.</p><p><br></p><h2>Other Information</h2><p dir="ltr">Published in: Biomedicines<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/biomedicines10051020" target="_blank">https://dx.doi.org/10.3390/biomedicines10051020</a></p>2022-04-28T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/biomedicines10051020https://figshare.com/articles/journal_contribution/Comparative_Transcriptome_Analysis_Reveals_That_Exendin-4_Improves_Steatosis_in_HepG2_Cells_by_Modulating_Signaling_Pathways_Related_to_Lipid_Metabolism/25624290CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/256242902022-04-28T03:00:00Z |
| spellingShingle | Comparative Transcriptome Analysis Reveals That Exendin-4 Improves Steatosis in HepG2 Cells by Modulating Signaling Pathways Related to Lipid Metabolism Khaoula Errafii (10914446) Biological sciences Biochemistry and cell biology Genetics steatosis GLP-1R agonist NAFLD HepG2 Exendin-4 |
| status_str | publishedVersion |
| title | Comparative Transcriptome Analysis Reveals That Exendin-4 Improves Steatosis in HepG2 Cells by Modulating Signaling Pathways Related to Lipid Metabolism |
| title_full | Comparative Transcriptome Analysis Reveals That Exendin-4 Improves Steatosis in HepG2 Cells by Modulating Signaling Pathways Related to Lipid Metabolism |
| title_fullStr | Comparative Transcriptome Analysis Reveals That Exendin-4 Improves Steatosis in HepG2 Cells by Modulating Signaling Pathways Related to Lipid Metabolism |
| title_full_unstemmed | Comparative Transcriptome Analysis Reveals That Exendin-4 Improves Steatosis in HepG2 Cells by Modulating Signaling Pathways Related to Lipid Metabolism |
| title_short | Comparative Transcriptome Analysis Reveals That Exendin-4 Improves Steatosis in HepG2 Cells by Modulating Signaling Pathways Related to Lipid Metabolism |
| title_sort | Comparative Transcriptome Analysis Reveals That Exendin-4 Improves Steatosis in HepG2 Cells by Modulating Signaling Pathways Related to Lipid Metabolism |
| topic | Biological sciences Biochemistry and cell biology Genetics steatosis GLP-1R agonist NAFLD HepG2 Exendin-4 |