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

Honglei Ji; Yizhe Chen; Judit Castillo-Armengol; René Dreos; Catherine Moret; Guy Niederhäuser; Brigitte Delacuisine; Isabel C Lopez-Mejia; Pierre-Damien Denechaud; Lluis Fajas

doi:10.1016/j.isci.2020.101163

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

iScience. 2020 Jun 26;23(6):101163. doi: 10.1016/j.isci.2020.101163. Epub 2020 May 15.

Affiliations

¹ Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
² Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland; College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
³ Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland; Institut National de la Santé et de la Recherche Médicale (Inserm), UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
⁴ Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland; Institut National de la Santé et de la Recherche Médicale (Inserm), Languedoc Roussillon, France. Electronic address: lluis.fajas@unil.ch.

Abstract

Cyclin-dependent kinases (CDKs) are emerging regulators of adipose tissue metabolism. Here we aimed to explore the role of CDK7 in thermogenic fat. We found that CDK7 brown adipose tissue (BAT)-specific knockout mice (Cdk7^bKO) have decreased BAT mass and impaired β3-adrenergic signaling and develop hypothermia upon cold exposure. We found that loss of CDK7 in BAT disrupts the induction of thermogenic genes in response to cold. However, Cdk7^bKO mice do not show systemic metabolic dysfunction. Increased expression of genes of the creatine metabolism compensates for the heat generation in the BAT of Cdk7^bKO mice in response to cold. Finally, we show that CDK7 is required for beta 3-adrenergic agonist-induced browning of white adipose tissue (WAT). Indeed, Cdk7 ablation in all adipose tissues (Cdk7^aKO) has impaired browning in WAT. Together, our results demonstrate that CDK7 is an important mediator of beta-adrenergic signaling in thermogenic brown and beige fat.

Keywords: Biological Sciences; Cell Biology; Endocrinology.