脂联素是白色脂肪组织中表达最丰富的细胞因子，在体内以三聚体、六聚体和高分子量多聚体等结构形式存在，具有抗糖尿病、抗动脉粥样硬化、抗肿瘤及保护心脏的作用。近年来研究表明CRP不仅仅是炎性标志物，它还是体内具有生物活性的炎症因子。我们前期研究发现，在胰岛素抵抗大鼠及人群，CRP表达增加，脂联素表达下降；在3T3-L1脂肪细胞，Northern、Western blot结果显示CRP以时间、剂量依赖方式抑制脂联素的表达和分泌；国外最新研究发现CRP转基因小鼠脂联素表达下降；以上研究结果表明CRP可能调控脂联素的表达和分泌。本项目拟进一步在细胞和整体水平观察CRP对脂联素表达和分泌的影响，并从信号途径入手，探明CRP直接调控脂联素表达和分泌的分子机制。本研究具有源头创新性，加强对脂联素基因表达调控的研究，有望绕开模拟脂联素复杂的高级结构的难题，找到一种新颖的药物以提高内源性脂联素浓度，对2型糖尿病、动脉粥样硬化、肿瘤等疾病的防治提供帮助。

Adiponectin, the most abundant protein secreted by white adipose tissue, is known for its involvement in obesity-related disorders such as insulin resistance, type 2 diabetes mellitus and atherosclerosis. Besides its well-known antidiabetic and antiatherosclerotic properties, accumulating evidence suggests that adiponectin may also have anticancer properties and be cardioprotective. It has been suggested that pharmacological strategies aimed at augmenting adiponectin levels or action may generate novel drugs to treat related diseases. However, the use of adiponectin as therapeutic targets is complicated by the presence of different adiponectin oligomeric isoforms. C-reactive protein (CRP) is one of the most sensitive inflammatory markers. Our group and others have reported that serum hs-CRP is inversely related to serum adiponectin in certain defined subjects. In our previous study, we found that the expression of CRP in liver and adipose tissues of insulin resistant rats induced by high fat diet(HFD) was increased, and adiponectin mRNA in adipose tissue was decreased. Northern and western blot analysis revealed that CRP-treatment inhibited adiponectin mRNA expression and secretion in a dose- and time-dependent manner in 3T3-L1 adipocytes. A recent study showed that human CRP overexpression facilitated the development of insulin resistance and hepatosteatosis with HFD in association with adiponectin down-regulation. Based on the findings mentioned above,It showed that the elevation of CRP level may lead to insulin resistance and artherosclerosis via inhibiting the expression and secretion of adiponectin. In the present study, we aim to investgate the molecular mechanism of CRP regulating adiponectin gene expression and secretion. Focusing on the upstream regulation of adiponectin by CRP may offer an elegant and novel therapeutic strategy that circumvents problems in designing drugs to mimic the complex higher order structure of adiponectin.