5-羟色胺(5-HT)已被证明可诱导肝细胞、脂肪细胞、肌管细胞产生胰岛素抵抗(IR)并加重非酒精性脂肪肝小鼠模型脂肪变性。我们首次发现，慢性应激、地塞米松或高脂饲料喂养诱导的IR与肝组织、内脏脂肪组织5-HT合成及5-HT2受体(5-HT2Rs)增加、骨骼肌5-HT2Rs增加密切相关。本项目旨在阐明这种外周5-HT系统改变是否为这些因素诱导IR的重要原因，阐明机制并弄清牵涉的关键的能量代谢调节信号通路。研究拟主要针对肝脏IR，次要涉及内脏脂肪组织及骨骼肌IR；应用“SD大鼠、野生型及基因敲除小鼠、原代肝细胞及脂肪细胞、基因沉默的细胞株”建立动物及细胞IR模型。研究成果对于“评价外周5-HT系统在IR发生时的作用、了解多种因素诱导IR是否存在普遍规律”有理论和临床意义，可能为代谢综合征、2型糖尿病的临床治疗提供新思路和新靶点。

It has been reported that 5-HT can induce insulin resistance (IR) in the hepatocytes, adipocytes and myotubes, and exacerbate hepatic steatosis in the mouse model of non-alcoholic fatty liver disease (NAFLD). We have found originally that chronic stress, dexamethasone (Dex) or high-fat diet (HFD) feeding-induced IR are closely associated with increased 5-HT synthesis and 5-HT 2 receptors (5-HT2Rs) in the hepatic tissue and visceral adipose tissue, and increased 5-HT2Rs in the skeletal muscle. The purposes of this study are to elucidate whether the alteration of peripheral 5-HT system is a crucial reason for aforementioned factors-induced IR, and to clarify the mechanism and key signaling pathways when 5-HT mediates glucocorticoids or HFD-induced IR. The research would chiefly focus on hepatic tissue IR, and also on visceral adipose tissue and skeletal muscle IR secondarily; We would make animals and cells IR models with SD rats, wild-type and gene knock-out mice, primary hepatocytes and adipocytes, and gene silencing cell lines. The research findings would have theoretical and clinical value for us to assess the role of peripheral 5-HT system in mediating IR generation and to understand whether has a common mechanism for various factor-inducing IR, this would also provide a new idea and target for the treatment of metobolism syndrome and type 2 diabetes mellitus.