Monocyte chemoattractant protein-induced protein 1 impairs adipogenesis in 3T3-L1 cells

Monocyte chemoattractant protein-induced protein I (MCPIP1) encoded by the ZC3H12a gene (also known as Regnase-1) is involved in the regulation of degradation of mRNA of inflammatory modulators and for processing of pre-miRNA. These functions depend on the presence of the PIN domain. Moreover, MCPIP1 was described as a negative regulator of NF-kappa B and AP-1 signaling pathways although mechanisms underlying such activity remain unknown. We aimed at determining the role of MCPIP1 in adipogenesis. Here, we present evidence that Mcpip1 transcription is transiently activated during 3T3-L1 transition from pre- to adipocytes. However Mcpipl protein expression is also strongly decreased at day one after induction of adipogenesis. Knockdown of Mcpipl results in an upregulation of C/EBP beta and PPAR gamma mRNAs, whereas overexpression of MCPIP1 reduces the level of both transcription factors and impairs adipogenesis. MCPIP1-dependend modulation of C/EBP beta and PPAR gamma levels results in a modulation of the expression of downstream controlled genes. In addition, decreased C/EBP beta, but not PPAR gamma, depends on the activity of the MCP1P1 PIN domain, which is responsible for RNase properties of this protein. Together, these data confirm that MCPIP1 is a key regulator of adipogenesis. (c) 2014 Elsevier B.V. All rights reserved.