RNAi profiling of mouse 3T3-L1 adipocytes knocked down for PPAR gamma returned the expression of most adipocyte genes towards preadipocyte levels

The nuclear receptor PPAR gamma is required for adipocyte differentiation, but its role in mature adipocytes is less clear. Here we report that knockdown of PPAR gamma expression in 3T3-L1 adipocytes returned the expression of most adipocyte genes towards preadipocyte levels. Consistently, down regulated but not up regulated genes showed strong enrichment of PPAR gamma binding. Surprisingly, not all adipocyte genes were reversed and the adipocyte morphology was maintained for an extended period after PPAR gamma depletion. To explain this, we focused on transcriptional regulators whose adipogenic regulation was not reversed upon PPAR gamma depletion. We identified GATA2, a transcription factor whose down-regulation early in adipogenesis is required for preadipocyte differentiation, remaining low after PPAR gamma knockdown. Forced expression of GATA2 in mature adipocytes complemented PPAR gamma depletion and impaired adipocyte functionality with a more preadipocyte- like gene expression profile. Ectopic expression of GATA2 in adipose tissue in vivo had similar effect on adipogenic gene expression. These results suggest that PPAR gamma-independent down regulation of GATA2 prevents reversion of mature adipocytes after PPAR gamma depletion. Experiment Overall Design: This dataset consists of three sample groups: preadipocytes, control siRNA treated adipocytes, and PPAR gamma siRNA treated adipocytes. Each sample group consists of three replicates samples. Each sample was hybridized to a separate array for a total of nine arrays. Experiment Overall Design: Technical replicates: Pread 1, Pread 2, Pread 3 Experiment Overall Design: Technical replicates: Cont siRNA 1, Cont siRNA 2, Cont siRNA 3 Experiment Overall Design: Technical replicates: PPAR gamma siRNA 1, PPAR gamma siRNA 2, PPAR gamma siRNA 3