%0 Journal Article
%T Insulin-induced serine 22 phosphorylation of retinoid X receptor alpha is dispensable for adipogenesis in brown adipocytes
%A Atefeh Rabiee
%A Brice Emanuelli
%A Goda Sinkevi£¿i¨±t£¿
%A Jacob Ardenkj£¿r-Larsen
%A Julia Villarroel
%A Kaja Rupar
%A Morten Lundh
%A Patricia S. S. Petersen
%A Romain Barr¨¨s
%J Adipocyte
%D 2020
%R https://doi.org/10.1080/21623945.2020.1747352
%X 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 (RXR¦Á) at S22 in mouse brown pre-adipocytes. Here, we show that insulin induces the phosphorylation of RXR¦Á at S22 in both brown precursor and mature adipocytes through a pathway involving ERK, downstream of IRS-1 and £¿2. We also found that RXR¦Á S22 phosphorylation is promoted by insulin and upon re-feeding in brown adipose tissue in vivo, and that insulin-stimulated S22 phosphorylation of RXR¦Á is dampened by diet-induced obesity. We used Rxra knockout cells re-expressing wild type (WT) or S22A non-phosphorylatable forms of RXR¦Á 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 RxraWT alleviated these effects. However, we observed no significant difference in cells re-expressing the RxraS22A mutant as compared with the cells re-expressing RxraWT. 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 RXR¦Á S22 phosphorylation in adipogenesis and transcription in differentiating brown pre-adipocytes
%U https://www.tandfonline.com/doi/full/10.1080/21623945.2020.1747352