Effect of FTY720P on lipid accumulation in HEPG2 cells
Abstract Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic lipid accumulation due to impaired lipid metabolism. Although a correlation was found between NAFLD and sphingosine-1-phosphate (S1P), the role of the sphingolipid remains controversial. The aim of this stud...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-46011-4 |
| _version_ | 1797559876613832704 |
|---|---|
| author | Reem Rida Sawsan Kreydiyyeh |
| author_facet | Reem Rida Sawsan Kreydiyyeh |
| author_sort | Reem Rida |
| collection | DOAJ |
| description | Abstract Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic lipid accumulation due to impaired lipid metabolism. Although a correlation was found between NAFLD and sphingosine-1-phosphate (S1P), the role of the sphingolipid remains controversial. The aim of this study was to investigate any involvement of S1P in steatosis using its analog FTY720P and HepG2 cells. Lipid accumulation was induced by incubating the cells in a mixture of oleic and palmitic acid, and was quantified using Oil Red O. The involvement of signaling mediators was studied using pharmacological inhibitors and western blot analysis. FTY720P increased lipid accumulation, but this increase wasn’t maintained in the presence of inhibitors of S1PR3, Gq, SREBP, mTOR, PI3K, and PPARγ indicating their involvement in the process. The results revealed that FTY720P binds to S1PR3 which activates sequentially Gq, PI3K, and mTOR leading to an increase in SREBP expression and PPARγ activation. It was concluded that in presence of a high level of fatty acids, lipid accumulation is increased in hepatocytes by the exogenously added FTY720P. |
| first_indexed | 2024-03-10T17:51:27Z |
| format | Article |
| id | doaj.art-047bebbee9b24da9924ab49ac2c914ab |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T17:51:27Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-047bebbee9b24da9924ab49ac2c914ab2023-11-20T09:19:20ZengNature PortfolioScientific Reports2045-23222023-11-0113111510.1038/s41598-023-46011-4Effect of FTY720P on lipid accumulation in HEPG2 cellsReem Rida0Sawsan Kreydiyyeh1Department of Biology, Faculty of Arts & Sciences, American University of BeirutDepartment of Biology, Faculty of Arts & Sciences, American University of BeirutAbstract Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic lipid accumulation due to impaired lipid metabolism. Although a correlation was found between NAFLD and sphingosine-1-phosphate (S1P), the role of the sphingolipid remains controversial. The aim of this study was to investigate any involvement of S1P in steatosis using its analog FTY720P and HepG2 cells. Lipid accumulation was induced by incubating the cells in a mixture of oleic and palmitic acid, and was quantified using Oil Red O. The involvement of signaling mediators was studied using pharmacological inhibitors and western blot analysis. FTY720P increased lipid accumulation, but this increase wasn’t maintained in the presence of inhibitors of S1PR3, Gq, SREBP, mTOR, PI3K, and PPARγ indicating their involvement in the process. The results revealed that FTY720P binds to S1PR3 which activates sequentially Gq, PI3K, and mTOR leading to an increase in SREBP expression and PPARγ activation. It was concluded that in presence of a high level of fatty acids, lipid accumulation is increased in hepatocytes by the exogenously added FTY720P.https://doi.org/10.1038/s41598-023-46011-4 |
| spellingShingle | Reem Rida Sawsan Kreydiyyeh Effect of FTY720P on lipid accumulation in HEPG2 cells Scientific Reports |
| title | Effect of FTY720P on lipid accumulation in HEPG2 cells |
| title_full | Effect of FTY720P on lipid accumulation in HEPG2 cells |
| title_fullStr | Effect of FTY720P on lipid accumulation in HEPG2 cells |
| title_full_unstemmed | Effect of FTY720P on lipid accumulation in HEPG2 cells |
| title_short | Effect of FTY720P on lipid accumulation in HEPG2 cells |
| title_sort | effect of fty720p on lipid accumulation in hepg2 cells |
| url | https://doi.org/10.1038/s41598-023-46011-4 |
| work_keys_str_mv | AT reemrida effectoffty720ponlipidaccumulationinhepg2cells AT sawsankreydiyyeh effectoffty720ponlipidaccumulationinhepg2cells |