SOD3在脂肪细胞中的功能及调控机制探讨

Studies have shown that SOD3 plays important protective roles in lung and vascular injury based on its anti-oxidation and anti-inflammation properties. Recent studies found that serum SOD3 levels from type 2 diabetes patients were significantly reduced and negatively correlated to BMI and insulin sensitivity. Our preliminary work found that SOD3 expressed at a high level in adipose tissue, with increased mRNA expression in differentiated adipocytes. The secretion of SOD3 from epidydimal adipose tissue from db/db mice was significantly reduced compared to wild type mice. To further investigate the role of SOD3 in obesity and its associated metabolic disorders, we propose to firstly study SOD3 expression in high-fat diet-induced obese mice. Secondly, we will use siRNA to downregulate SOD3 gene expressions in human preadipocytes and adipocytes and study whether SOD3 knockdown affects preadipocytes differentiation, adipocytes insulin sensitivity and endocrine function. Lastly, we will feed SOD3-/- mice with high-fat diet and study the role of SOD3 in adipose tissue in vivo. In summary, the proposed project will provide the scientific evidence for SOD3 as a potential secreted protein by adipose tissue to protect against obesity and its associated metabolic diseases.

早期研究表明，SOD3具有抗氧化和抗炎性，在肺和血管系统起重要保护作用。近年来一些研究发现，二型糖尿病患者血浆中SOD3水平显著降低，并与BMI和胰岛素敏感性成负相关。肝脏过表达SOD3的小鼠可抵抗高脂诱导的肥胖及脂肪组织炎症，提高胰岛素敏感性。申请人前期工作发现，SOD3是脂肪组织分泌蛋白，与脂肪细胞分化有关，并在db/db小鼠脂肪组织中分泌水平降低。为进一步研究SOD3在肥胖及其相关代谢疾病中的作用，本课题将首先利用高脂诱导的肥胖小鼠模型，研究SOD3在肥胖小鼠脂肪组织中的表达，明确SOD3与肥胖的关系。其次，下调人前脂肪细胞和脂肪细胞SOD3，探索其在脂肪细胞分化、胰岛素敏感性和内分泌功能方面的作用。最后，对SOD3基因敲除小鼠进行高脂饲养，研究SOD3在体内脂肪组织中的功能。以上研究为探讨SOD3能否作为潜在的脂肪组织分泌的抗击肥胖及相关代谢疾病的保护性分子提供科学依据。