Integrative genomics reveals MCPIP1 role in adipogenesis and adipocytes metabolism

Obesity is considered as a serious chronic disease which is associated with greater risk of developing cardiovascular diseases, non-alcoholic fatty liver disease or type 2 diabetes. Monocyte chemoattractant protein-1-induced protein-1 (MCPIP1) also called as Regnase-1 is a RNase decreasing stability of transcripts coding for inflammation-related proteins. In addition, MCPIP1 plays an important role in the regulation of adipogenesis in vitro by reducing the expression of key transcription factors during adipocyte differentiation including C/EBPß and PPAR?. Here we report RNA-Seq and proteome analysis of 3T3-L1 adipocytes overexpressing wild-type MCPIP1 (WTMCPIP1) and mutant MCPIP1 (D141NMCPIP1) at day 2 and 4 of differentiation, respectively. The RNA-Seq analysis followed by confirmatory Q-RT-PCR analysis revealed that elevated MCPIP1 level in 3T3-L1 adipocytes upregulates transcripts encoding proteins involved in signal transmission and cellular remodeling and downregulates transcripts of factors mainly involved in metabolism. This data are consistent with our LC-MS/MS analysis where we showed that MCPIP1 expressing adipocytes exhibit upregulation of proteins involved in cellular organization and movement and decreased level of proteins involved in lipid and carbohydrate metabolism. Moreover, MCPIP1 adipocytes are characterized by decreased level of Glut4 and impaired glucose uptake. Overall, our ?ndings demonstrated that MCPIP1 is an important regulator of adipogenesis and adipocytes metabolism.