AIMP1/p43 negatively regulates adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma

Abstract

Adipogenesis is known to be controlled by the concerted actions of transcription factors and co-regulators. However, little is known about the regulation mechanism of transcription factors that control adipogenesis. In addition, the adipogenic roles of translational factors remain unclear. Here, we show that aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1), an auxiliary factor that is associated with a macromolecular tRNA synthetase complex, negatively regulates adipogenesis via a direct interaction with the DNA-binding domain of peroxisome proliferator-activated receptor γ (PPARγ). AIMP1 expression increased during adipocyte differentiation. Adipogenesis was augmented in AIMP1-deficient cells, as compared with control cells. AIMP1 exhibited high affinity for active PPARγ and interacted with the DNA-binding domain of PPARγ, thereby inhibiting its transcriptional activity. Thus, AIMP1 appears to function as a novel inhibitor of PPARγ that regulates adipocyte differentiation by preventing the transcriptional activation of PPARγ.