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Oncogenic steroid receptor coactivator-3 is a key regulator of the white adipogenic program

Jean-Francois Louet1, Agnès Coste, Larbi Amazit

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Proceedings of the National Academy of Sciences of the United States of America
|November 14, 2006
PubMed

Insights

Steroid receptor coactivator-3 (SRC-3) is essential for white adipocyte development and regulates key genes like PPARgamma2. Its absence impairs fat cell formation, impacting body weight and adipose tissue mass.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Endocrinology

Background:

  • White adipocytes are central to metabolic disorders like obesity and diabetes.
  • Dysfunctional regulatory pathways in adipocytes contribute to various diseases.
  • The role of specific coactivators in adipogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the role of steroid receptor coactivator-3 (SRC-3) in white adipocyte development.
  • To determine the molecular mechanisms by which SRC-3 influences adipogenesis.
  • To assess the impact of SRC-3 deficiency on adipose tissue mass and body weight.

Main Methods:

  • Utilized SRC-3 knockout (SRC-3(-/-)) mouse embryonic fibroblasts to study adipocyte differentiation.
  • Analyzed nuclear levels of SRC-3 during adipocyte differentiation.
  • Examined body weight, adipose tissue mass, and gene expression (PPARgamma2) in SRC-3(-/-) animals.
  • Investigated the interaction of SRC-3 with transcription factors like CAAT/enhancer-binding protein.

Main Results:

  • SRC-3(-/-) mouse embryonic fibroblasts exhibited severely impaired adipocyte differentiation.
  • Re-expression of SRC-3 restored adipocyte differentiation.
  • SRC-3 accumulated in the nucleus during early adipocyte differentiation.
  • SRC-3(-/-) animals showed reduced body weight and adipose tissue mass.
  • Expression of peroxisome proliferator-activated receptor gamma2 (PPARgamma2) was significantly decreased in SRC-3(-/-) animals.
  • SRC-3 acted synergistically with CAAT/enhancer-binding protein to regulate PPARgamma2 gene expression.

Conclusions:

  • SRC-3 is a critical regulator of white adipocyte development.
  • SRC-3 plays a key role in controlling the expression of PPARgamma2, a master regulator of adipogenesis.
  • SRC-3 integrates the transcriptional network controlling adipogenesis, highlighting its importance in metabolic regulation.

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