Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0174761
Title: Regulation of white and brown adipocyte differentiation by RhoGAP DLC1
Authors: Sim C.K.
Kim S.-Y.
Brunmeir R. 
Zhang Q.
Li H.
Dharmasegaran D.
Leong C.
Lim Y.Y.
Han W. 
Xu F. 
Keywords: F actin
peroxisome proliferator activated receptor gamma
Rho kinase
DLC1 protein, human
guanosine triphosphatase activating protein
peroxisome proliferator activated receptor gamma
rho GTPase-activating protein
small interfering RNA
tumor suppressor protein
adipogenesis
animal cell
animal tissue
Article
brown adipocyte
brown adipose tissue
cell differentiation
controlled study
DLC1 gene
embryo
female
fibroblast
gene
gene control
gene expression
gene identification
gene silencing
limit of quantitation
male
mitochondrial respiration
mouse
nonhuman
phenotype
protein binding
white adipocyte
brown adipocyte
cell culture
cell differentiation
chromatin immunoprecipitation
cytology
genetics
human
indirect calorimetry
metabolism
oxygen consumption
physiology
Western blotting
white adipocyte
Adipocytes, Brown
Adipocytes, White
Adipogenesis
Blotting, Western
Calorimetry, Indirect
Cell Differentiation
Cells, Cultured
Chromatin Immunoprecipitation
GTPase-Activating Proteins
Humans
Oxygen Consumption
PPAR gamma
RNA, Small Interfering
Tumor Suppressor Proteins
Issue Date: 2017
Citation: Sim C.K., Kim S.-Y., Brunmeir R., Zhang Q., Li H., Dharmasegaran D., Leong C., Lim Y.Y., Han W., Xu F. (2017). Regulation of white and brown adipocyte differentiation by RhoGAP DLC1. PLoS ONE 12 (3) : e0174761. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0174761
Rights: Attribution 4.0 International
Abstract: 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 superenhancer associated gene in both white and brown adipocytes through analyzing the genome-wide binding profiles of PPAR?, 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, PPAR? 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 PPAR? and Rho pathways. © 2017 Sim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161199
ISSN: 19326203
DOI: 10.1371/journal.pone.0174761
Rights: Attribution 4.0 International
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