Insulin-induced serine 22 phosphorylation of retinoid X receptor alpha is dispensable for adipogenesis in brown adipocytes. (1st January 2020)

• Record Type: Journal Article
• Authors: Ardenkjær-Larsen, Jacob; Rupar, Kaja; Sinkevičiūtė, Goda; Petersen, Patricia S. S.; Villarroel, Julia; Lundh, Morten; Barrès, Romain; Rabiee, Atefeh; Emanuelli, Brice
• Is Part Of: Adipocyte. Volume 9:Number 1(2020)
• Page Start: 142
• Page End: 152
• Publication Date: 2020-01-01
• Subjects: Retinoid X receptor alpha -- insulin -- phosphorylation -- adipose tissue -- transcriptional regulation; Fat cells -- Periodicals; Adipocytes -- Periodicals; 611.018276
• DOI: 10.1080/21623945.2020.1747352
• Languages: English
• ISSNs: 2162-3945

Abstract

ABSTRACT: Insulin action initiates a series of phosphorylation events regulating cellular differentiation, growth and metabolism. We have previously discovered, in a mass spectrometry-based phosphoproteomic study, that insulin/IGF-1 signalling induces phosphorylation of retinoid x receptor alpha (RXRα) at S22 in mouse brown pre-adipocytes. Here, we show that insulin induces the phosphorylation of RXRα at S22 in both brown precursor and mature adipocytes through a pathway involving ERK, downstream of IRS-1 and −2. We also found that RXRα S22 phosphorylation is promoted by insulin and upon re-feeding in brown adipose tissue in vivo, and that insulin-stimulated S22 phosphorylation of RXRα is dampened by diet-induced obesity. We used Rxra knockout cells re-expressing wild type (WT) or S22A non-phosphorylatable forms of RXRα to further characterize the role of S22 in brown adipocytes. Knockout of Rxra in brown pre-adipocytes resulted in decreased lipid accumulation and adipogenic gene expression during differentiation, and re-expression of Rxra WT alleviated these effects. However, we observed no significant difference in cells re-expressing the Rxra S22A mutant as compared with the cells re-expressing Rxra WT. Furthermore, comparison of gene expression during adipogenesis in the WT and S22A re-expressing cells by RNA sequencing revealed similar transcriptomic profiles. Thus, our data propose a dispensable role for RXRα S22 phosphorylation in adipogenesis and transcription in differentiating brown pre-adipocytes.