In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 22, No. 10 ( 2018-10), p. 4709-4720
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2018.22.issue-10
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2076114-4
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