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miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression

Eun Kyung Lee1, Mi Jeong Lee, Kotb Abdelmohsen

  • 1Laboratory of Molecular Biology and Immunology, NIA-IRP, NIH, Baltimore, Maryland 21224, USA.

Molecular and Cellular Biology
|December 8, 2010
PubMed

Insights

MicroRNAs regulate fat cell development. Lower levels of microRNA-130 (miR-130) in obese women correlate with higher peroxisome proliferator-activated receptor γ (PPARγ) and impaired fat cell formation, suggesting a role in obesity.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Adipose tissue development is a complex process regulated by gene expression.
  • MicroRNAs (miRNAs) are key posttranscriptional regulators influencing mammalian cell differentiation.
  • The specific role of miRNAs in human adipogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the role of microRNAs in human adipogenesis.
  • To identify specific microRNAs affecting the differentiation of preadipocytes into adipocytes.
  • To determine the molecular mechanisms by which microRNAs regulate adipogenesis, focusing on peroxisome proliferator-activated receptor γ (PPARγ).

Main Methods:

  • Profiling microRNA abundance during human preadipocyte differentiation.
  • Manipulating microRNA levels (overexpression and reduction) to assess effects on adipogenesis.
  • Quantifying peroxisome proliferator-activated receptor γ (PPARγ) expression and its regulation by microRNAs.
  • Analyzing microRNA and PPARγ mRNA levels in adipose tissue from obese and nonobese women.

Main Results:

  • MicroRNA-130 (miR-130) abundance varied during adipogenesis.
  • Overexpression of miR-130 impaired adipogenesis, while its reduction enhanced it.
  • miR-130 directly targeted and repressed PPARγ expression at both coding and 3' untranslated regions.
  • Obese women exhibited lower miR-130 and higher PPARγ mRNA levels in adipose tissue compared to nonobese women.

Conclusions:

  • miR-130 acts as a negative regulator of adipogenesis by repressing PPARγ biosynthesis.
  • Dysregulation of the miR-130/PPARγ axis may contribute to the pathogenesis of human obesity.
  • This study identifies a novel molecular mechanism linking microRNA regulation to adipose tissue development and obesity.

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