SRA Regulates Adipogenesis by Modulating p38/JNK Phosphorylation and Stimulating Insulin Receptor Gene Expression and Downstream Signaling

Shannon Liu, Ruichuan Xu, Isabelle Gerin, William P. Cawthorn, Ormond A. MacDougald, Xiao-Wei Chen, Alan R. Saltiel, Ronald J. Koenig, Bin Xu

Research output: Contribution to journalArticlepeer-review

Abstract

The Steroid Receptor RNA Activator (SRA) enhances adipogenesis and increases both glucose uptake and phosphorylation of Akt and FOXO1 in response to insulin. To assess the mechanism, we differentiated ST2 mesenchymal precursor cells that did or did not overexpress SRA into adipocytes using combinations of methylisobutylxanthine, dexamethasone and insulin. These studies showed that SRA overexpression promotes full adipogenesis in part by stimulation of insulin/insulin-like growth factor-1 (IGF-1) signaling. SRA overexpression inhibited phosphorylation of p38 mitogen activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) in the early differentiation of ST2 cells. Conversely, knockdown of endogenous SRA in 3T3-L1 cells increased phosphorylation of JNK. Knockdown of SRA in mature 3T3-L1 adipocytes reduced insulin receptor (IR) mRNA and protein levels, which led to decreased autophosphorylation of IR beta and decreased phosphorylation of insulin receptor substrate-1 (IRS-1) and Akt. This likely reflects a stimulatory role of SRA on IR transcription, as transfection studies showed that SRA increased expression of an IR promoter-luciferase reporter construct.

Original languageEnglish
Article number95416
Number of pages10
JournalPLoS ONE
Volume9
Issue number4
DOIs
Publication statusPublished - 17 Apr 2014

Keywords

  • RNA ACTIVATOR SRA
  • ADIPOCYTE DIFFERENTIATION
  • MUSCLE DIFFERENTIATION
  • PROTEIN SRAP
  • RESISTANCE
  • KINASE
  • GLUCOSE
  • BINDING
  • CELLS
  • MICE

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