An Evil-C/EBPβ Complex Controls Perwdsome Proliferator-Activated Receptor γ2 Gene Expression To Initiate White Fat Cell Differentiation

Fibroblastic preadipocyte cells are recruited to differentiate into new adipocytes during the formation and hyperplastic growth of white adipose tissue. Peroxisome proliferator-activated receptor gamma (PPAR gamma), the master regulator of adipogenesis, is expressed at low levels in preadipocytes, and its levels increase dramatically and rapidly during the differentiation process. However, the mechanisms controlling the dynamic and selective expression of PPAR gamma in the adipocyte lineage remain largely unknown. We show here that the zinc finger protein Evil increases in preadipocytes at the onset of differentiation prior to increases in PPAR gamma levels. Evil expression converts nonadipogenic cells into adipocytes via an increase in the predifferentiation levels of PPAR gamma 2, the adipose-selective isoform of PPAR gamma. Conversely, loss of Evil in preadipocytes blocks the induction of PPAR gamma 2 and suppresses adipocyte differentiation. Evil binds with C/EBP beta to regulatory sites in the Ppar gamma locus at early stages of adipocyte differentiation, coincident with the induction of Ppar gamma 2 expression. These results indicate that Evil is a key regulator of adipogenic competency.