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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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Autores principales: Sim, Choon Kiat, Kim, Sun-Yee, Brunmeir, Reinhard, Zhang, Qiongyi, Li, Hongyu, Dharmasegaran, Dharmini, Leong, Carol, Lim, Ying Yan, Han, Weiping, Xu, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373604/
https://www.ncbi.nlm.nih.gov/pubmed/28358928
http://dx.doi.org/10.1371/journal.pone.0174761
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author Sim, Choon Kiat
Kim, Sun-Yee
Brunmeir, Reinhard
Zhang, Qiongyi
Li, Hongyu
Dharmasegaran, Dharmini
Leong, Carol
Lim, Ying Yan
Han, Weiping
Xu, Feng
author_facet Sim, Choon Kiat
Kim, Sun-Yee
Brunmeir, Reinhard
Zhang, Qiongyi
Li, Hongyu
Dharmasegaran, Dharmini
Leong, Carol
Lim, Ying Yan
Han, Weiping
Xu, Feng
author_sort Sim, Choon Kiat
collection PubMed
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.
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spelling pubmed-53736042017-04-07 Regulation of white and brown adipocyte differentiation by RhoGAP DLC1 Sim, Choon Kiat Kim, Sun-Yee Brunmeir, Reinhard Zhang, Qiongyi Li, Hongyu Dharmasegaran, Dharmini Leong, Carol Lim, Ying Yan Han, Weiping Xu, Feng PLoS One Research Article 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. Public Library of Science 2017-03-30 /pmc/articles/PMC5373604/ /pubmed/28358928 http://dx.doi.org/10.1371/journal.pone.0174761 Text en © 2017 Sim et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sim, Choon Kiat
Kim, Sun-Yee
Brunmeir, Reinhard
Zhang, Qiongyi
Li, Hongyu
Dharmasegaran, Dharmini
Leong, Carol
Lim, Ying Yan
Han, Weiping
Xu, Feng
Regulation of white and brown adipocyte differentiation by RhoGAP DLC1
title 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_short Regulation of white and brown adipocyte differentiation by RhoGAP DLC1
title_sort regulation of white and brown adipocyte differentiation by rhogap dlc1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373604/
https://www.ncbi.nlm.nih.gov/pubmed/28358928
http://dx.doi.org/10.1371/journal.pone.0174761
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