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CDK7 Mediates the Beta-Adrenergic Signaling in Thermogenic Brown and White Adipose Tissues

Honglei Ji1, Yizhe Chen2, Judit Castillo-Armengol1

  • 1Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.

Iscience
|May 29, 2020
PubMed

Insights

Cyclin-dependent kinase 7 (CDK7) regulates thermogenic fat metabolism. Loss of CDK7 impairs cold-induced heat production and fat browning, highlighting its role in beta-adrenergic signaling.

Area of Science:

  • Metabolic regulation
  • Adipose tissue biology
  • Thermogenesis

Background:

  • Cyclin-dependent kinases (CDKs) are increasingly recognized for their roles in regulating adipose tissue metabolism.
  • The specific function of CDK7 in thermogenic fat (brown adipose tissue, BAT) remains largely unexplored.

Purpose of the Study:

  • To investigate the role of CDK7 in the function and metabolism of brown adipose tissue.
  • To determine CDK7's involvement in beta-adrenergic signaling and thermogenesis in response to cold exposure.

Main Methods:

  • Generation and analysis of brown adipose tissue-specific (Cdk7bKO) and all adipose tissue-specific (Cdk7aKO) knockout mouse models.
  • Assessment of BAT mass, β3-adrenergic signaling, thermogenic gene expression, and response to cold exposure.
  • Evaluation of white adipose tissue (WAT) browning induced by beta-3 adrenergic agonists.

Main Results:

  • Cdk7bKO mice exhibited reduced BAT mass, impaired β3-adrenergic signaling, and hypothermia upon cold exposure.
  • Loss of CDK7 in BAT disrupted the induction of thermogenic genes but was compensated by creatine metabolism genes.
  • Cdk7aKO mice showed impaired browning of WAT in response to beta-3 adrenergic agonists, indicating CDK7's role in beige fat activation.

Conclusions:

  • CDK7 is crucial for mediating β-adrenergic signaling in both brown and beige adipose tissues.
  • CDK7 plays a significant role in regulating thermogenesis and adipose tissue browning.
Keywords:
Biological SciencesCell BiologyEndocrinology

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