Open AccessNR 4A1 retards adipocyte differentiation or maturation via enhancing GATA 2 and p53 expression
Author(s) -
Qin Dandan,
Yang Yingfeng,
Pu Zeqing,
Liu Dong,
Yu Cong,
Gao Peng,
Chen Jicui,
Zong Chen,
Zhang Yuchao,
Li Xia,
Wang Xiangdong,
Liu Yuantao
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13715
Subject(s) - transcription factor , adipogenesis , biology , peroxisome proliferator activated receptor , receptor , nuclear receptor , chemistry , microbiology and biotechnology , biochemistry , gene
Nuclear receptor subfamily 4 group A member 1 ( NR 4A1) is an orphan nuclear receptor with diverse functions. It has been reported that NR 4A1, as a transcriptional activator, is implicated in glucose and lipid metabolism. The aim of this study was to investigate the regulatory role of NR 4A1 in adipogenesis and explore the underlying mechanisms. Quantitative real‐time PCR and Western blotting were used to analyse the expression of genes involved in synthesis and mobilization of fats in vivo and in vitro. Dual‐luciferase reporter assay was conducted to study the regulatory mechanisms of NR 4A1. Our data from in vivo study confirmed that NR 4A1 knockout ( KO ) mice fed with high‐fat diet were more prone to obesity, and gene expression levels of PPAR γ and FAS were increased in KO mice compared to controls; our data from in vitro study showed that NR 4A1 overexpression in 3T3‐L1 pre‐adipocytes inhibited adipogenesis. Moreover, NR 4A1 enhanced GATA binding protein 2 ( GATA 2) expression, which in turn inhibited peroxisome proliferator‐activated receptor γ ( PPAR γ); NR 4A1 inhibited sterol regulatory element binding transcription factor 1 ( SREBP 1) and its downstream gene fatty acid synthase ( FAS ) by up‐regulating p53. NR 4A1 inhibits the differentiation and lipid accumulation of adipocytes by enhancing the expression of GATA 2 and p53.