Obesity is considered a serious chronic disease, associated with an increased risk of developing cardiovascular diseases, non-alcoholic fatty liver disease and type 2 diabetes. Monocyte chemoattractant protein-1-induced protein-1 (MCPIP1) is an 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, including C/EBPβ. To elucidate the role of MCPIP1 in adipocyte biology, we performed RNA-Seq and proteome analysis in 3T3-L1 adipocytes overexpressing wild-type (_WTMCPIP1) and the mutant form of MCPIP1 protein (_D141NMCPIP1). Our RNA-Seq analysis followed by confirmatory Q-RT-PCR revealed that elevated MCPIP1 levels in 3T3-L1 adipocytes upregulated transcripts encoding proteins involved in signal transmission and cellular remodeling and downregulated transcripts of factors involved in metabolism. These data are consistent with our proteomic analysis, which showed that MCPIP1 expressing adipocytes exhibit upregulation of proteins involved in cellular organization and movement and decreased levels of proteins involved in lipid and carbohydrate metabolism. Moreover, MCPIP1 adipocytes are characterized by decreased level of insulin receptor, reduced insulin-induced Akt phosphorylation, as well as depleted Glut4 level and impaired glucose uptake. Overexpression of Glut4 in 3T3-L1 cells expressed _WTMCPIP1 rescued adipogenesis. Interestingly, we found decreased level of MCPIP1 along with an increase in body mass index in subcutaneous adipose tissue. The presented data show a novel role of MCPIP1 in modulating insulin sensitivity in adipocytes. Overall, our findings demonstrate that MCPIP1 is an important regulator of adipogenesis and adipocyte metabolism.

肥胖被认为是一种严重的慢性疾病，与罹患心血管疾病，非酒精性脂肪肝疾病和2型糖尿病的风险增加有关。单核细胞趋化蛋白-1诱导蛋白1（MCPIP1）是一种RNase，可降低编码炎症相关蛋白的转录本的稳定性。此外，MCPIP1通过减少关键转录因子（包括C /EBPβ）的表达，在体外调节脂肪形成中起着重要作用。为了阐明MCPIP1的在脂肪细胞生物学中的作用，我们进行了RNA测序和在3T3-L1蛋白质组分析脂肪细胞过表达野生型（_WT MCPIP1）和MCPIP1蛋白的突变体形式（_D141NMCPIP1）。我们的RNA-Seq分析以及随后的确认性Q-RT-PCR表明，升高的3T3-L1脂肪细胞中MCPIP1水平上调了编码信号传导和细胞重塑的蛋白质的转录本，并下调了参与代谢的因子的转录本。这些数据与我们的蛋白质组学分析一致，后者表明表达MCPIP1的脂肪细胞显示参与细胞组织和运动的蛋白质上调，而参与脂质和碳水化合物代谢的蛋白质水平降低。此外，MCPIP1脂肪细胞的特征是胰岛素受体水平降低，胰岛素诱导的Akt磷酸化水平降低，Glut4水平降低和葡萄糖摄取受损。Glut4在3T3-L1细胞中过表达_WTMCPIP1挽救了脂肪形成。有趣的是，我们发现皮下脂肪组织中MCPIP1的水平下降，同时体重指数也增加。提出的数据显示了MCPIP1在调节脂肪细胞中胰岛素敏感性方面的新作用。总体而言，我们的发现表明MCPIP1是脂肪形成和脂肪细胞代谢的重要调节剂。