The LIM protein Ajuba promotes adipogenesis by enhancing PPARγ and p300/CBP interaction

Adipocytes play a vital role in energy homeostasis and adipogenesis is a hierarchically regulated cellular differentiation process, in which the precursor mesenchymal stem cells are differentiated into mature adipocytes. Here, we report Ajuba is an important regulator of adipocyte differentiation by functioning as an obligate co-activator of PPARγ. Ajuba binds the DNA-binding domain of PPARγ via its preLIM region in a ligand-independent manner. Depletion of Ajuba in 3T3-L1 cells decreases PPARγ target gene expression and results in delayed adipogenic differentiation. Conversely, stable overexpression of Ajuba in 3T3-L1 cells increases PPARγ target gene expression and accelerates adipogenic differentiation. Mechanistic investigations demonstrate that Ajuba recruits p300/CBP via its LIM domain and facilitates p300/CBP binding to PPARγ. Moreover, Ajuba, PPARγ, p300/CBP can cooperatively occupy the PPARγ target promoters and concomitantly increases histone acetylation at these loci. Collectively, these data suggest that Ajuba is a co-activator constitutively associated with PPARγ and may be a potential therapeutic target for PPARγ-mediated metabolic disorders.