Abstract
Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an orphan nuclear receptor with diverse functions. It has been reported that NR4A1, as a transcriptional activator, is implicated in glucose and lipid metabolism. The aim of this study was to investigate the regulatory role of NR4A1 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 NR4A1. Our data from in vivo study confirmed that NR4A1 knockout (KO) mice fed with high‐fat diet were more prone to obesity, and gene expression levels of PPARγ and FAS were increased in KO mice compared to controls; our data from in vitro study showed that NR4A1 overexpression in 3T3‐L1 pre‐adipocytes inhibited adipogenesis. Moreover, NR4A1 enhanced GATA binding protein 2 (GATA2) expression, which in turn inhibited peroxisome proliferator‐activated receptor γ (PPARγ); NR4A1 inhibited sterol regulatory element binding transcription factor 1 (SREBP1) and its downstream gene fatty acid synthase (FAS) by up‐regulating p53. NR4A1 inhibits the differentiation and lipid accumulation of adipocytes by enhancing the expression of GATA2 and p53.
Highlights
Obesity has drawn more and more attention as it is becoming a severe public health problem
We found that NR4A1 overexpression inhibited adipogenesis in 3T3-L1 pre-adipocytes
In consistency with previous study, our results showed that NR4A1 KO mice fed with high-fat diet were inclined to develop obesity compared to wild-type mice (WT mice)
Summary
Obesity has drawn more and more attention as it is becoming a severe public health problem. Fatty acids are essential for energy production and the synthesis of most lipids involved in cell structure and cellular signalling. Factors involved in lipolytic process include adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), lipoprotein lipase (LPL) and other molecules. Some enzymes have been reported to account for complete hydrolysis of triacylglycerol (TAG) molecules in cellular lipid stores: ATGL selectively performs the first and rate-limiting step hydrolysing TAGs to generate diacylglycerols (DAGs) and non-esterified fatty acids. The fate of obesity formation depends on the balance between the processes of adipogenesis or lipid accumulation and lipolysis. SREBP1c regulates the expression of genes or enzymes for glucose metabolism and lipid production.[16]. We investigated the role of NR4A1 in adipogenesis and explored the possible mechanisms
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