Liraglutide Exerts Protective Effects by Downregulation of <i>PPARγ</i>, <i>ACSL1</i> and <i>SREBP-1c</i> in Huh7 Cell Culture Models of Non-Alcoholic Steatosis and Drug-Induced Steatosis
(1) Background: With the aging of the population and polypharmacy encountered in the elderly, drug-induced steatosis (DIS) has become frequent cause of non-alcoholic steatosis (NAS). Indeed, NAS and DIS may co-exist, making the ability to distinguish between the entities ever more important. The aim...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-08-01
|
| Series: | Current Issues in Molecular Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1467-3045/44/8/239 |
| _version_ | 1797410786616803328 |
|---|---|
| author | Tea Omanovic Kolaric Tomislav Kizivat Vjera Mihaljevic Milorad Zjalic Ines Bilic-Curcic Lucija Kuna Robert Smolic Aleksandar Vcev George Y. Wu Martina Smolic |
| author_facet | Tea Omanovic Kolaric Tomislav Kizivat Vjera Mihaljevic Milorad Zjalic Ines Bilic-Curcic Lucija Kuna Robert Smolic Aleksandar Vcev George Y. Wu Martina Smolic |
| author_sort | Tea Omanovic Kolaric |
| collection | DOAJ |
| description | (1) Background: With the aging of the population and polypharmacy encountered in the elderly, drug-induced steatosis (DIS) has become frequent cause of non-alcoholic steatosis (NAS). Indeed, NAS and DIS may co-exist, making the ability to distinguish between the entities ever more important. The aim of our study was to study cell culture models of NAS and DIS and determine the effects of liraglutide (LIRA) in those models. (2) Methods: Huh7 cells were treated with oleic acid (OA), or amiodarone (AMD) to establish models of NAS and DIS, respectively. Cells were treated with LIRA and cell viability was assessed by MTT, lipid accumulation by Oil-Red-O staining and triglyceride assay, and intracellular signals involved in hepatosteatosis were quantitated by RT-PCR. (3) Results: After exposure to various OA and AMD concentrations, those that achieved 80% of cells viabilities were used in further experiments to establish NAS and DIS models using 0.5 mM OA and 20 µM AMD, respectively. In both models, LIRA increased cell viability (<i>p</i> < 0.01). Lipid accumulation was increased in both models, with microsteatotic pattern in DIS, and macrosteatotic pattern in NAS which corresponds to greater triglyceride accumulation in latter. LIRA ameliorated these changes (<i>p</i> < 0.001), and downregulated expression of lipogenic <i>ACSL1</i>, <i>PPARγ</i>, and <i>SREBP-1c</i> pathways in the liver (<i>p</i> < 0.01) (4) Conclusions: LIRA ameliorates hepatocyte steatosis in Huh7 cell culture models of NAS and DIS. |
| first_indexed | 2024-03-09T04:35:15Z |
| format | Article |
| id | doaj.art-c815af59f67c496a9a50dce02969cadf |
| institution | Directory Open Access Journal |
| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-09T04:35:15Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj.art-c815af59f67c496a9a50dce02969cadf2023-12-03T13:29:02ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-08-014483465348010.3390/cimb44080239Liraglutide Exerts Protective Effects by Downregulation of <i>PPARγ</i>, <i>ACSL1</i> and <i>SREBP-1c</i> in Huh7 Cell Culture Models of Non-Alcoholic Steatosis and Drug-Induced SteatosisTea Omanovic Kolaric0Tomislav Kizivat1Vjera Mihaljevic2Milorad Zjalic3Ines Bilic-Curcic4Lucija Kuna5Robert Smolic6Aleksandar Vcev7George Y. Wu8Martina Smolic9Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, Crkvena 21, 31000 Osijek, CroatiaDepartment of Nuclear Medicine and Oncology, Faculty of Medicine Osijek, J. Huttlera 4, 31000 Osijek, CroatiaDepartment of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, Crkvena 21, 31000 Osijek, CroatiaDepartment of Molecular Medicine and Biotechnology, Faculty of Medicine Rijeka, B. Branchetta 20, 51000 Rijeka, CroatiaDepartment of Pharmacology, Faculty of Medicine Osijek, J. Huttlera 4, 31000 Osijek, CroatiaDepartment of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, Crkvena 21, 31000 Osijek, CroatiaDepartment of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, Crkvena 21, 31000 Osijek, CroatiaDepartment of Pathophysiology and Physiology with Immunology, Faculty of Dental Medicine and Health Osijek, Crkvena 21, 31000 Osijek, CroatiaDepartment of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, 135 Dowling Way, Farmington, CT 06030, USADepartment of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health Osijek, Crkvena 21, 31000 Osijek, Croatia(1) Background: With the aging of the population and polypharmacy encountered in the elderly, drug-induced steatosis (DIS) has become frequent cause of non-alcoholic steatosis (NAS). Indeed, NAS and DIS may co-exist, making the ability to distinguish between the entities ever more important. The aim of our study was to study cell culture models of NAS and DIS and determine the effects of liraglutide (LIRA) in those models. (2) Methods: Huh7 cells were treated with oleic acid (OA), or amiodarone (AMD) to establish models of NAS and DIS, respectively. Cells were treated with LIRA and cell viability was assessed by MTT, lipid accumulation by Oil-Red-O staining and triglyceride assay, and intracellular signals involved in hepatosteatosis were quantitated by RT-PCR. (3) Results: After exposure to various OA and AMD concentrations, those that achieved 80% of cells viabilities were used in further experiments to establish NAS and DIS models using 0.5 mM OA and 20 µM AMD, respectively. In both models, LIRA increased cell viability (<i>p</i> < 0.01). Lipid accumulation was increased in both models, with microsteatotic pattern in DIS, and macrosteatotic pattern in NAS which corresponds to greater triglyceride accumulation in latter. LIRA ameliorated these changes (<i>p</i> < 0.001), and downregulated expression of lipogenic <i>ACSL1</i>, <i>PPARγ</i>, and <i>SREBP-1c</i> pathways in the liver (<i>p</i> < 0.01) (4) Conclusions: LIRA ameliorates hepatocyte steatosis in Huh7 cell culture models of NAS and DIS.https://www.mdpi.com/1467-3045/44/8/239NASamiodaroneliraglutideHuh7 cell line |
| spellingShingle | Tea Omanovic Kolaric Tomislav Kizivat Vjera Mihaljevic Milorad Zjalic Ines Bilic-Curcic Lucija Kuna Robert Smolic Aleksandar Vcev George Y. Wu Martina Smolic Liraglutide Exerts Protective Effects by Downregulation of <i>PPARγ</i>, <i>ACSL1</i> and <i>SREBP-1c</i> in Huh7 Cell Culture Models of Non-Alcoholic Steatosis and Drug-Induced Steatosis Current Issues in Molecular Biology NAS amiodarone liraglutide Huh7 cell line |
| title | Liraglutide Exerts Protective Effects by Downregulation of <i>PPARγ</i>, <i>ACSL1</i> and <i>SREBP-1c</i> in Huh7 Cell Culture Models of Non-Alcoholic Steatosis and Drug-Induced Steatosis |
| title_full | Liraglutide Exerts Protective Effects by Downregulation of <i>PPARγ</i>, <i>ACSL1</i> and <i>SREBP-1c</i> in Huh7 Cell Culture Models of Non-Alcoholic Steatosis and Drug-Induced Steatosis |
| title_fullStr | Liraglutide Exerts Protective Effects by Downregulation of <i>PPARγ</i>, <i>ACSL1</i> and <i>SREBP-1c</i> in Huh7 Cell Culture Models of Non-Alcoholic Steatosis and Drug-Induced Steatosis |
| title_full_unstemmed | Liraglutide Exerts Protective Effects by Downregulation of <i>PPARγ</i>, <i>ACSL1</i> and <i>SREBP-1c</i> in Huh7 Cell Culture Models of Non-Alcoholic Steatosis and Drug-Induced Steatosis |
| title_short | Liraglutide Exerts Protective Effects by Downregulation of <i>PPARγ</i>, <i>ACSL1</i> and <i>SREBP-1c</i> in Huh7 Cell Culture Models of Non-Alcoholic Steatosis and Drug-Induced Steatosis |
| title_sort | liraglutide exerts protective effects by downregulation of i pparγ i i acsl1 i and i srebp 1c i in huh7 cell culture models of non alcoholic steatosis and drug induced steatosis |
| topic | NAS amiodarone liraglutide Huh7 cell line |
| url | https://www.mdpi.com/1467-3045/44/8/239 |
| work_keys_str_mv | AT teaomanovickolaric liraglutideexertsprotectiveeffectsbydownregulationofippargiiacsl1iandisrebp1ciinhuh7cellculturemodelsofnonalcoholicsteatosisanddruginducedsteatosis AT tomislavkizivat liraglutideexertsprotectiveeffectsbydownregulationofippargiiacsl1iandisrebp1ciinhuh7cellculturemodelsofnonalcoholicsteatosisanddruginducedsteatosis AT vjeramihaljevic liraglutideexertsprotectiveeffectsbydownregulationofippargiiacsl1iandisrebp1ciinhuh7cellculturemodelsofnonalcoholicsteatosisanddruginducedsteatosis AT miloradzjalic liraglutideexertsprotectiveeffectsbydownregulationofippargiiacsl1iandisrebp1ciinhuh7cellculturemodelsofnonalcoholicsteatosisanddruginducedsteatosis AT inesbiliccurcic liraglutideexertsprotectiveeffectsbydownregulationofippargiiacsl1iandisrebp1ciinhuh7cellculturemodelsofnonalcoholicsteatosisanddruginducedsteatosis AT lucijakuna liraglutideexertsprotectiveeffectsbydownregulationofippargiiacsl1iandisrebp1ciinhuh7cellculturemodelsofnonalcoholicsteatosisanddruginducedsteatosis AT robertsmolic liraglutideexertsprotectiveeffectsbydownregulationofippargiiacsl1iandisrebp1ciinhuh7cellculturemodelsofnonalcoholicsteatosisanddruginducedsteatosis AT aleksandarvcev liraglutideexertsprotectiveeffectsbydownregulationofippargiiacsl1iandisrebp1ciinhuh7cellculturemodelsofnonalcoholicsteatosisanddruginducedsteatosis AT georgeywu liraglutideexertsprotectiveeffectsbydownregulationofippargiiacsl1iandisrebp1ciinhuh7cellculturemodelsofnonalcoholicsteatosisanddruginducedsteatosis AT martinasmolic liraglutideexertsprotectiveeffectsbydownregulationofippargiiacsl1iandisrebp1ciinhuh7cellculturemodelsofnonalcoholicsteatosisanddruginducedsteatosis |