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 γ

Pappachan E Kolattukudy,Craig W Younce,Asim Azfer

doi:10.1074/jbc.m109.025320

Pappachan E Kolattukudy, Craig W Younce + Show 1 more

Open Access

https://doi.org/10.1074/jbc.m109.025320

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Abstract

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) beta, C/EBPdelta, and C/EBPalpha and peroxisome proliferator-activated receptor gamma (PPARgamma). Currently, PPARgamma is universally accepted as the master regulator that is necessary and sufficient to induce adipogenesis as no known factor can induce adipogenesis without PPARgamma. We present evidence that a novel zinc finger protein, MCP-1-induced protein (MCPIP), can induce adipogenesis without PPARgamma. 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 PPARgamma. 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/EBPbeta, C/EBPdelta, C/EBPalpha, and PPARgamma and adipogenesis without any other inducer. Forced expression of MCPIP induces expression of the C/EBP family of transcription factors and adipogenesis in PPARgamma(-/-) mouse embryonic fibroblasts. Thus, MCPIP is a newly identified protein that can induce adipogenesis without PPARgamma.

Highlights

The incidence of obesity and associated diseases is increasing dramatically throughout the world
We recently reported that MCP-1 binding to CCR2 leads to the induction of a novel zinc finger protein, called MCP-1-induced protein (MCPIP), that can induce cell death [8] or differentiation leading to angiogenesis [10]
Detected [11], and in a tissue engineering model of adipogenesis MCP-1 treatment was reported to increase adipose tissue mass in vivo [9]. In view of these observations that suggest the possibility of a role for MCP-1 in adipogenesis, we tested whether differentiation of 3T3-L1 cells into adipocytes involves MCP-1

Summary

Introduction

The incidence of obesity and associated diseases is increasing dramatically throughout the world. Transcript levels of the adipogenesis markers C/EBP␤, C/EBP␦, C/EBP␣, and PPAR␥ were measured using real time RT-PCR (* ϭ p Ͻ 0.02; # ϭ p Ͻ 0.03). MCP-1 treatment induced expression of the C/EBP family of transcription factors and PPAR␥ that is known to be induced during differentiation of 3T3-L1 cells into adipocytes (Fig. 1B).

Results

Conclusion