Inhibition of mevalonate pathway prevents adipocyte browning in mouse and men by affecting protein prenylation

Research in recent years focusing on brown adipose tissue functionality emphasizes an important role of this organ in energy homeostasis. Utilizing a transcriptome analysis of human brown and white adipose tissue, we identified an enrichment of the mevalonate pathway in BAT suggesting its importance in regulating BAT function. By inhibiting different intermediate steps of the mevalonate pathway, using pharmacological and genetic approaches in vitro and in vivo, we show that mevalonate pathway controls brown adipocyte functionality in mouse and men by providing geranylgeranyl pyrophosphate, the substrate for protein prenylation of small GTP-binding proteins. Taken together, our study demonstrates the importance of the mevalonate pathway for brown fat functionality in mouse and men.