Mediating lipid biosynthesis: Implications for cardiovascular disease

Dysregulation of lipid homeostasis is a risk factor for cardiovascular disease (CVD). Thus, understanding the molecular mechanisms of maintaining lipid homeostasis may aid the discovery of novel targets for treating CVD. MED15 and cyclin-dependent kinase-8 (CDK8) are subunits of the Mediator complex, which contains multiple proteins and functions as a transcriptional cofactor. Mediator can positively or negatively regulate gene expression, depending on the contexts and its associated transcription factors. Recent studies revealed a critical role of MED15 and CDK8 in regulating sterol regulatory element-binding protein (SREBP) transcription factors, which are master activators for genes that are responsible for lipid biosynthesis. Here, we review the function of MED15 and CDK8 in regulating lipid homeostasis and discuss the implications for CVD.