MED1 is a lipogenesis coactivator required for postnatal adipose expansion

Abstract

MED1 often serves as a surrogate of the general transcription coactivator complex Mediator for identifying active enhancers. MED1 is required for phenotypic conversion of fibroblasts to adipocytes in vitro but its role in adipose development and expansion in vivo has not been reported. Here we report that MED1 is dispensable for adipose development in mice. Instead, MED1 is required for postnatal adipose expansion and the induction of de novo lipogenesis (DNL) genes after pups switch diet from high-fat maternal milk to carbohydrate-based chow. During adipogenesis, MED1 is dispensable for induction of lineage-determining transcription factors (TFs) PPAR{gamma} and C/EBP but is required for lipid accumulation in the late phase of differentiation. Mechanistically, MED1 controls the induction of DNL genes by facilitating lipogenic TF ChREBP-dependent recruitment of Mediator to active enhancers. Together, our findings identify a cell- and gene-specific regulatory role of MED1 as a lipogenesis coactivator required for postnatal adipose expansion. O_LIMED1 is largely dispensable for adipogenesis and embryonic development of adipose tissue C_LIO_LIMED1 is required for postnatal adipose expansion C_LIO_LIMED1 is required for DNL gene expression in adipocytes C_LIO_LIMED1 controls DNL gene transcription by facilitating ChREBP-dependent Mediator binding to active enhancers C_LI