CCR4-NOT2 Promotes the Differentiation and Lipogenesis of 3T3-L1 Adipocytes via Upregulation of PPARγ, CEBPα and Inhibition of P-GSK3α/β and β-Catenin

Abstract

Background/Aims: Though CCR4-NOT2 (CNOT2), one of CCR4-NOT complex subunits, was known to be involved in metastasis and apoptosis through transcription and mRNA degradation, its other biological function is poorly understood so far. The aim of this study is to elucidate the molecular role of CNOT2 in the differentiation process of 3T3-L1 preadipocytes. Methods and Results: CNOT2 was overexpressed during the differentiation process of 3T3-L1 preadipocytes. Consistently, mRNA levels of CNOT2, adiponectin, adiponectin 2, PPARγ and CEBPα were enhanced in 3T3-L1 adipocytes. Conversely, CNOT2 depletion by siRNA transfection also reversed the activation of PPARγ and CEBPα and inhibition of GSK3α/β and β-catenin at the protein level in 3T3-L1 preadipocytes. Immunofluorescence assay revealed that CNOT2 was colocalized with PPARγ, but not with CEBPα in 3T3-L1 adipocyte. Consistently, IP western blots revealed that CNOT2 interacted with PPARγ in 3T3-L1 adipocyte. Conclusion: Our findings demonstrate that CNOT2 promotes the differentiation of 3T3-L1 preadipocytes via upregulation of PPARγ, and CEBPα and inhibition of GSK3α/β and β-catenin signaling as a potent molecular target for obesity.

Keywords

• Adipogenesis
• 3T3-L1
• PPARγ
• CEBPα
• Obesity
• CNOT2