肥胖及其伴发疾病如糖尿病、心血管病的发病率逐年攀升，严重危害人类健康。肥胖的发生与脂肪细胞功能障碍、免疫细胞浸润及脂肪组织慢性低水平炎症反应有关，但机制尚未完全阐明。CREG是一种小分子的分泌型糖蛋白，在促进分化、对抗炎症及维持心血管稳态中起重要作用。我们的预实验研究发现：（1）肥胖患者大网膜脂肪组织CREG表达较对照组显著降低；（2）在高脂喂养的小鼠肥胖模型中，与野生型小鼠相比，CREG杂合子小鼠体重显著增加、胰岛素抵抗加重、有益的脂肪因子表达降低，且调控糖、脂代谢的重要因子PPARβ/δ表达下降。据此，我们提出假设：脂肪细胞中CREG表达下降可能导致脂肪细胞功能障碍，从而引起肥胖；这一作用可能通过调控PPARβ/δ实现。本研究拟利用脂肪特异性CREG敲除小鼠建立高脂喂养肥胖模型，明确CREG作用；然后在体外利用脂肪细胞进一步探讨机制。本研究可能加深对肥胖机制的理解，并为其治疗提供靶点。

The prevalence of obesity and its debilitating comorbidities including diabetes and cardiovascular disease are increasing, resulting in severe threaten to human being. Adipocyte dysfunction, immunocyte infiltration and chronic low grade inflammation in adipose tissue are major features of obesity, but the underlying mechanism remains largely unclear. CREG, a small secreted glycoprotein, has essential roles in promoting differentiation, antagonizing inflammation and maintaining homeostasis of cardiovascular system. Our preliminary data showed that (1) expression of CREG in omentum adipose tissue in obese patients was lower than in lean controls; (2) in a high fat diet induced obesity mouse model, compared to wild type controls, CREG heterozygote mouse showed increased body weight, worsen insulin resistance and decreased favorable adipokine expression. Interestingly, expression of PPARβ/δ, an important factor regulating lipid and glucose metabolism, was also parallelly down regulated in CREG heterozygote group. Taken together, we hypothesized that down-regulation of CREG in adipocyte may cause adipocyte dysfunction and subsequent obesity, which was possibly mediated by regulation of PPARβ/δ pathway. To test this hypothesis, we plan to firstly determine role of CREG in obesity by adopting an in vivo high fat diet induced obesity model in mouse with adipocyte specific knockout of CREG; then detailed molecular mechanism will be explored in an in vitro cell model of adipocyte. This study may deepen understanding of obesity pathogenesis, and providing potential target for treatment of obesity.