MCP-1 (Monocyte Chemotactic Protein-1)-induced Protein, a Recently Identified Zinc Finger Protein, Induces Adipogenesis in 3T3-L1 Pre-adipocytes without Peroxisome Proliferator-activated Receptor Î

• Published in: The Journal of biological chemistry 2009-10, Vol.284 (40), p.27620
• Main Authors: Craig W. Younce, Asim Azfer, Pappachan E. Kolattukudy
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.025320

Adipogenesis is a key differentiation process relevant to obesity and associated diseases such as type 2 diabetes. This process involves temporally regulated genes controlled by a set of transcription factors, CCAAT/enhancer-binding proteins (C/EBP) β, C/EBPδ, and C/EBPα and peroxisome proliferator-activated receptor γ (PPARγ). Currently, PPARγ is universally accepted as the master regulator that is necessary and sufficient to induce adipogenesis as no known factor can induce adipogenesis without PPARγ. We present evidence that a novel zinc finger protein, MCP-1-induced protein (MCPIP), can induce adipogenesis without PPARγ. Classical adipogenesis-inducing medium induces MCP-1 production and expression of MCPIP in 3T3-L1 cells before the induction of the C/EBP family of transcription factors and PPARγ. Knockdown of MCPIP prevents their expression and adipogenesis as measured by expression of adipocyte markers and lipid droplet accumulation. Treatment of 3T3-L1 cells with MCP-1 or forced expression of MCPIP induces expression of C/EBPβ, C/EBPδ, C/EBPα, and PPARγ and adipogenesis without any other inducer. Forced expression of MCPIP induces expression of the C/EBP family of transcription factors and adipogenesis in PPARγ −/− mouse embryonic fibroblasts. Thus, MCPIP is a newly identified protein that can induce adipogenesis without PPARγ.