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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Duy Trong Vien Diep, Kyungki Hong, Triyeng Khun, Mei Zheng, Asad ul-Haq, Hee-Sook Jun, Young-Bum Kim, Kwang-Hoon Chun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bc681f112e094eaa874a9aaf9fccaa17
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:bc681f112e094eaa874a9aaf9fccaa17
record_format	dspace
spelling	oai:doaj.org-article:bc681f112e094eaa874a9aaf9fccaa172021-12-02T15:08:51ZAnti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells10.1038/s41598-018-20821-32045-2322https://doaj.org/article/bc681f112e094eaa874a9aaf9fccaa172018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-20821-3https://doaj.org/toc/2045-2322Abstract 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.Duy Trong Vien DiepKyungki HongTriyeng KhunMei ZhengAsad ul-HaqHee-Sook JunYoung-Bum KimKwang-Hoon ChunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	anti-adipogenic effects of kd025 (slx-2119), a rock2-specific inhibitor, in 3t3-l1 cells
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/bc681f112e094eaa874a9aaf9fccaa17
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
_version_	1718388023398236160

Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells

Ejemplares similares