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Updated: May 1, 2026

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
SRA regulates adipogenesis by modulating p38/JNK phosphorylation and stimulating insulin receptor gene expression and
Shannon Liu1, Ruichuan Xu1, Isabelle Gerin2
1Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical Center, Ann Arbor, Michigan, United States of America.
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 IRβ 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.
Insights
Steroid Receptor RNA Activator (SRA) promotes adipogenesis by enhancing insulin signaling. SRA also regulates key proteins involved in glucose metabolism and cell differentiation.
Area of Science:
- Molecular Biology
- Cell Biology
- Metabolic Research
Background:
- Steroid Receptor RNA Activator (SRA) is implicated in adipogenesis and glucose metabolism.
- Insulin signaling pathways are crucial for adipocyte differentiation and function.
Purpose of the Study:
- To elucidate the mechanism by which SRA influences adipogenesis and insulin signaling.
- To investigate the role of SRA in regulating insulin receptor (IR) expression and downstream signaling.
Main Methods:
- Overexpression of SRA in ST2 mesenchymal precursor cells and differentiation into adipocytes.
- Knockdown of endogenous SRA in 3T3-L1 cells.
- Analysis of protein phosphorylation (Akt, FOXO1, p38 MAPK, JNK, IRβ, IRS-1).
- Reporter assays to assess SRA's effect on IR promoter activity.
Main Results:
- SRA overexpression promoted adipogenesis and enhanced insulin/IGF-1 signaling.
- SRA modulated phosphorylation of MAPK pathway components (p38 MAPK, JNK) during differentiation.
- SRA knockdown in mature adipocytes reduced IR mRNA and protein, impairing insulin signaling.
- SRA was shown to stimulate IR gene transcription.
Conclusions:
- SRA plays a significant role in promoting adipogenesis through stimulation of insulin signaling.
- SRA positively regulates insulin receptor expression at the transcriptional level.
- SRA influences key signaling pathways involved in cellular differentiation and metabolic regulation.
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