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

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 <sup>bKO</sup> ) 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 <sup>bKO</sup> 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 <sup>bKO</sup> 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 <sup>aKO</sup> ) 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