肥胖已成为全球性流行疾病，研究成脂分化，寻找预防和治疗肥胖的新靶标和新机制十分必要。BMP-SMAD信号通路对成脂分化命运决定至关重要，但是该通路是如何被调控的机制尚未完全阐明。我们前期研究发现，QKI可以调控多个系统的细胞分化（Gastroenterology，2010；Mol Biol Cell，2012）。我们正在进行的研究发现，QKI也是促进成脂分化的必需分子；可以调控其潜在靶基因Spectrin-βII的可变剪接，促进其可变剪接体βSpIIΣ2的表达。而βSpIIΣ2正是调控BMP-SMAD信号通路的重要分子。综上我们推测，QKI通过调控Spectrin-βII分子的可变剪接，从而调控BMP-SMAD信号通路促进了成脂分化。本项目拟在前期研究的基础上，阐明QKI在成脂分化中作用及机制，加深我们对成脂分化转录后调控的认识，为肥胖及其相关代谢性疾病的预防和治疗提供新策略和新靶点。

Obesity has reached epidemic proportions worldwide. Understanding the mechanisms implicated in the regulation of adipocyte differentiation should help elucidate obesity development and find new approaches for preventing and treating obesity. BMP-SMAD signaling pathway plays a critical role in adipogenesis. However, the mechanisms regulating this pathway are poorly understood.We have reported that QKI regulates the differentiation of colon epithelial cells and macrophages (Gastroenterology, 2010; Mol Biol Cell, 2012). In the present study, we found that QKI is required for adipocyte differention. Furthermore, lacking of QKI leads to alterations in Spectrin-βII alternative splicing and the diminished expression of βSpIIΣ2 which plays a key role in BMP signaling pathway. Based on these results, we propose that QKI is required for adipocyte differentiation, and it may play its role in adipogenesis through regulating alternative splicing of Spectrin-βII. This research will help elucidate obesity development, thus provide new therapeutic strategies for the prevention and treatment of obesity and its related metabolic disorders.