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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
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Protein kinase D regulates the adiponectin gene expression through phosphorylation of AP-2: a common pathway to the

Noriyuki Iwamoto1, Shinji Yokoyama

  • 1Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467 8601, Japan.

Atherosclerosis
|February 25, 2011
PubMed

Insights

Protein kinase D (PKD) regulates adiponectin gene expression. Inhibiting PKD increases adiponectin, suggesting a therapeutic target for type-2 diabetes and metabolic disorders.

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Metabolic Diseases

Background:

  • Activator protein AP-2β is linked to type-2 diabetes and suppresses adiponectin gene expression.
  • Protein kinase D (PKD) phosphorylates AP-2α, negatively regulating ATP-binding cassette A1 (ABCA1) gene expression.

Purpose of the Study:

  • Investigate PKD's role in regulating adiponectin gene expression.
  • Determine if PKD modulates AP-2β DNA binding to the adiponectin promoter.

Main Methods:

  • Cell culture experiments with siRNA knockdown of PKD.
  • Analysis of adiponectin mRNA and promoter activity.
  • Western blotting and chromatin immunoprecipitation (ChIP) assays.
  • In vivo studies using a selective PKD inhibitor (Gö6983) in mice.

Main Results:

  • PKD knockdown increased adiponectin mRNA, promoter activity, and secretion, while reducing fat accumulation.
  • PKD activators decreased adiponectin expression; this effect was blocked by PKD inhibition.
  • ChIP analysis showed PKD inhibition reduced AP-2β binding to the adiponectin promoter.
  • Gö6983 administration increased adiponectin expression in mice.

Conclusions:

  • PKD negatively regulates adiponectin gene expression by modulating AP-2β DNA binding.
  • PKD acts as a common regulator for both AP-2α and AP-2β, influencing ABCA1 and adiponectin gene expression via phosphorylation.
  • Targeting PKD may offer a therapeutic strategy for metabolic disorders like type-2 diabetes.

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