Regulation of white and brown adipocyte differentiation by RhoGAP DLC1.
Adipose tissues constitute an important component of metabolism, the dysfunction of which can cause obesity and type II diabetes. Here we show that differentiation of white and brown adipocytes requires Deleted in Liver Cancer 1 (DLC1), a Rho GTPase Activating Protein (RhoGAP) previously studied for...
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doaj-efa2d7dd47994cac81a9b2e9561046902020-11-25T01:22:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01123e017476110.1371/journal.pone.0174761Regulation of white and brown adipocyte differentiation by RhoGAP DLC1.Choon Kiat SimSun-Yee KimReinhard BrunmeirQiongyi ZhangHongyu LiDharmini DharmasegaranCarol LeongYing Yan LimWeiping HanFeng XuAdipose tissues constitute an important component of metabolism, the dysfunction of which can cause obesity and type II diabetes. Here we show that differentiation of white and brown adipocytes requires Deleted in Liver Cancer 1 (DLC1), a Rho GTPase Activating Protein (RhoGAP) previously studied for its function in liver cancer. We identified Dlc1 as a super-enhancer associated gene in both white and brown adipocytes through analyzing the genome-wide binding profiles of PPARγ, the master regulator of adipogenesis. We further observed that Dlc1 expression increases during differentiation, and knockdown of Dlc1 by siRNA in white adipocytes reduces the formation of lipid droplets and the expression of fat marker genes. Moreover, knockdown of Dlc1 in brown adipocytes reduces expression of brown fat-specific genes and diminishes mitochondrial respiration. Dlc1-/- knockout mouse embryonic fibroblasts show a complete inability to differentiate into adipocytes, but this phenotype can be rescued by inhibitors of Rho-associated kinase (ROCK) and filamentous actin (F-actin), suggesting the involvement of Rho pathway in DLC1-regulated adipocyte differentiation. Furthermore, PPARγ binds to the promoter of Dlc1 gene to regulate its expression during both white and brown adipocyte differentiation. These results identify DLC1 as an activator of white and brown adipocyte differentiation, and provide a molecular link between PPARγ and Rho pathways.http://europepmc.org/articles/PMC5373604?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Choon Kiat Sim Sun-Yee Kim Reinhard Brunmeir Qiongyi Zhang Hongyu Li Dharmini Dharmasegaran Carol Leong Ying Yan Lim Weiping Han Feng Xu |
spellingShingle |
Choon Kiat Sim Sun-Yee Kim Reinhard Brunmeir Qiongyi Zhang Hongyu Li Dharmini Dharmasegaran Carol Leong Ying Yan Lim Weiping Han Feng Xu Regulation of white and brown adipocyte differentiation by RhoGAP DLC1. PLoS ONE |
author_facet |
Choon Kiat Sim Sun-Yee Kim Reinhard Brunmeir Qiongyi Zhang Hongyu Li Dharmini Dharmasegaran Carol Leong Ying Yan Lim Weiping Han Feng Xu |
author_sort |
Choon Kiat Sim |
title |
Regulation of white and brown adipocyte differentiation by RhoGAP DLC1. |
title_short |
Regulation of white and brown adipocyte differentiation by RhoGAP DLC1. |
title_full |
Regulation of white and brown adipocyte differentiation by RhoGAP DLC1. |
title_fullStr |
Regulation of white and brown adipocyte differentiation by RhoGAP DLC1. |
title_full_unstemmed |
Regulation of white and brown adipocyte differentiation by RhoGAP DLC1. |
title_sort |
regulation of white and brown adipocyte differentiation by rhogap dlc1. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2017-01-01 |
description |
Adipose tissues constitute an important component of metabolism, the dysfunction of which can cause obesity and type II diabetes. Here we show that differentiation of white and brown adipocytes requires Deleted in Liver Cancer 1 (DLC1), a Rho GTPase Activating Protein (RhoGAP) previously studied for its function in liver cancer. We identified Dlc1 as a super-enhancer associated gene in both white and brown adipocytes through analyzing the genome-wide binding profiles of PPARγ, the master regulator of adipogenesis. We further observed that Dlc1 expression increases during differentiation, and knockdown of Dlc1 by siRNA in white adipocytes reduces the formation of lipid droplets and the expression of fat marker genes. Moreover, knockdown of Dlc1 in brown adipocytes reduces expression of brown fat-specific genes and diminishes mitochondrial respiration. Dlc1-/- knockout mouse embryonic fibroblasts show a complete inability to differentiate into adipocytes, but this phenotype can be rescued by inhibitors of Rho-associated kinase (ROCK) and filamentous actin (F-actin), suggesting the involvement of Rho pathway in DLC1-regulated adipocyte differentiation. Furthermore, PPARγ binds to the promoter of Dlc1 gene to regulate its expression during both white and brown adipocyte differentiation. These results identify DLC1 as an activator of white and brown adipocyte differentiation, and provide a molecular link between PPARγ and Rho pathways. |
url |
http://europepmc.org/articles/PMC5373604?pdf=render |
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