摘要：SummaryCyclin-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 (Cdk7bKO) 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,Cdk7bKOmice do not show systemic metabolic dysfunction. Increased expression of genes of the creatine metabolism compensates for the heat generation in the BAT ofCdk7bKOmice in response to cold. Finally, we show that CDK7 is required for beta 3-adrenergic agonist-induced browning of white adipose tissue (WAT). Indeed,Cdk7ablation in all adipose tissues (Cdk7aKO) 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.Graphical AbstractDisplay OmittedHighlights•CDK7 brown fat-specific knockout mice are cold intolerant•CDK7 is required for β-adrenergic signaling activation in response to cold•Creatine metabolism compensates for the impairment of thermogenesis inCdk7bKOmice•CDK7 mediates in the response to β3-adrenoceptor agonist in white adipose tissueBiological Sciences; Endocrinology; Cell Biology
