Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells
Abstract Adipose tissue is a specialized organ that synthesizes and stores fat. During adipogenesis, Rho and Rho-associated kinase (ROCK) 2 are inactivated, which enhances the expression of pro-adipogenic genes and induces the loss of actin stress fibers. Furthermore, pan ROCK inhibitors enhance adi...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2018-02-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-20821-3 |
| _version_ | 1818998763767726080 |
|---|---|
| author | Duy Trong Vien Diep Kyungki Hong Triyeng Khun Mei Zheng Asad ul-Haq Hee-Sook Jun Young-Bum Kim Kwang-Hoon Chun |
| author_facet | Duy Trong Vien Diep Kyungki Hong Triyeng Khun Mei Zheng Asad ul-Haq Hee-Sook Jun Young-Bum Kim Kwang-Hoon Chun |
| author_sort | Duy Trong Vien Diep |
| collection | DOAJ |
| description | Abstract Adipose tissue is a specialized organ that synthesizes and stores fat. During adipogenesis, Rho and Rho-associated kinase (ROCK) 2 are inactivated, which enhances the expression of pro-adipogenic genes and induces the loss of actin stress fibers. Furthermore, pan ROCK inhibitors enhance adipogenesis in 3T3-L1 cells. Here, we show that KD025 (formerly known as SLx-2119), a ROCK2-specific inhibitor, suppresses adipogenesis in 3T3-L1 cells partially through a ROCK2-independent mechanism. KD025 downregulated the expression of key adipogenic transcription factors PPARγ and C/EBPα during adipogenesis in addition to lipogenic factors FABP4 and Glut4. Interestingly, adipogenesis was blocked by KD025 during days 1~3 of differentiation; after differentiation terminated, lipid accumulation was unaffected. Clonal expansion occurred normally in KD025-treated cells. These results suggest that KD025 could function during the intermediate stage after clonal expansion. Data from depletion of ROCKs showed that KD025 suppressed cell differentiation partially independent of ROCK’s activity. Furthermore, no further loss of actin stress fibers emerged in KD025-treated cells during and after differentiation compared to control cells. These results indicate that in contrast to the pro-adipogenic effect of pan-inhibitors, KD025 suppresses adipogenesis in 3T3-L1 cells by regulating key pro-adipogenic factors. This outcome further implies that KD025 could be a potential anti-adipogenic/obesity agent. |
| first_indexed | 2024-12-20T22:06:42Z |
| format | Article |
| id | doaj.art-bc681f112e094eaa874a9aaf9fccaa17 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T22:06:42Z |
| publishDate | 2018-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-bc681f112e094eaa874a9aaf9fccaa172022-12-21T19:25:15ZengNature PortfolioScientific Reports2045-23222018-02-018111410.1038/s41598-018-20821-3Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cellsDuy Trong Vien Diep0Kyungki Hong1Triyeng Khun2Mei Zheng3Asad ul-Haq4Hee-Sook Jun5Young-Bum Kim6Kwang-Hoon Chun7Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon UniversityGachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon UniversityGachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon UniversityGachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon UniversityGachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon UniversityGachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon UniversityDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, BostonGachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon UniversityAbstract Adipose tissue is a specialized organ that synthesizes and stores fat. During adipogenesis, Rho and Rho-associated kinase (ROCK) 2 are inactivated, which enhances the expression of pro-adipogenic genes and induces the loss of actin stress fibers. Furthermore, pan ROCK inhibitors enhance adipogenesis in 3T3-L1 cells. Here, we show that KD025 (formerly known as SLx-2119), a ROCK2-specific inhibitor, suppresses adipogenesis in 3T3-L1 cells partially through a ROCK2-independent mechanism. KD025 downregulated the expression of key adipogenic transcription factors PPARγ and C/EBPα during adipogenesis in addition to lipogenic factors FABP4 and Glut4. Interestingly, adipogenesis was blocked by KD025 during days 1~3 of differentiation; after differentiation terminated, lipid accumulation was unaffected. Clonal expansion occurred normally in KD025-treated cells. These results suggest that KD025 could function during the intermediate stage after clonal expansion. Data from depletion of ROCKs showed that KD025 suppressed cell differentiation partially independent of ROCK’s activity. Furthermore, no further loss of actin stress fibers emerged in KD025-treated cells during and after differentiation compared to control cells. These results indicate that in contrast to the pro-adipogenic effect of pan-inhibitors, KD025 suppresses adipogenesis in 3T3-L1 cells by regulating key pro-adipogenic factors. This outcome further implies that KD025 could be a potential anti-adipogenic/obesity agent.https://doi.org/10.1038/s41598-018-20821-3 |
| spellingShingle | Duy Trong Vien Diep Kyungki Hong Triyeng Khun Mei Zheng Asad ul-Haq Hee-Sook Jun Young-Bum Kim Kwang-Hoon Chun Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells Scientific Reports |
| title | Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells |
| title_full | Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells |
| title_fullStr | Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells |
| title_full_unstemmed | Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells |
| title_short | Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells |
| title_sort | anti adipogenic effects of kd025 slx 2119 a rock2 specific inhibitor in 3t3 l1 cells |
| url | https://doi.org/10.1038/s41598-018-20821-3 |
| work_keys_str_mv | AT duytrongviendiep antiadipogeniceffectsofkd025slx2119arock2specificinhibitorin3t3l1cells AT kyungkihong antiadipogeniceffectsofkd025slx2119arock2specificinhibitorin3t3l1cells AT triyengkhun antiadipogeniceffectsofkd025slx2119arock2specificinhibitorin3t3l1cells AT meizheng antiadipogeniceffectsofkd025slx2119arock2specificinhibitorin3t3l1cells AT asadulhaq antiadipogeniceffectsofkd025slx2119arock2specificinhibitorin3t3l1cells AT heesookjun antiadipogeniceffectsofkd025slx2119arock2specificinhibitorin3t3l1cells AT youngbumkim antiadipogeniceffectsofkd025slx2119arock2specificinhibitorin3t3l1cells AT kwanghoonchun antiadipogeniceffectsofkd025slx2119arock2specificinhibitorin3t3l1cells |