半胱氨酸双加氧酶Cdo1在白色脂肪组织棕色化中的作用和分子机制研究

白色脂肪组织的棕色化能增强能量消耗、改善代谢，是防治肥胖的新策略。半胱氨酸双加氧酶Cdo1是催化半胱氨酸分解、牛磺酸生成的关键酶，在脂肪组织中有较丰富的表达。然而Cdo1在脂肪组织中的作用鲜有报道。我们前期研究发现：1、冷暴露后小鼠皮下白色脂肪组织中Cdo1的表达显著上调；2、在C3H10T1/2脂肪细胞中敲低Cdo1，抑制了细胞耗氧、脂解和葡萄糖摄取，而过表达Cdo1后则促进了细胞耗氧、脂解和葡萄糖摄取；3、利用腺病毒在小鼠皮下白色脂肪组织中过表达Cdo1，提高了皮下脂肪组织产热能力，增强了皮下脂肪组织棕色化基因表达、耗氧及葡萄糖摄取。本项目拟结合细胞/分子生物学实验和小鼠模型，深入研究Cdo1在白色脂肪组织棕色化中的作用和分子机制，为调控白色脂肪组织棕色化进而防治肥胖提供新的思路和分子靶点。

Promoting the browning of white adipose tissue helps to burn energy, to improve metabolism and is considered to be a new strategy to combat obesity. Cysteine dioxygenase 1 (Cdo1) is a key enzyme in catabolizing cysteine and in synthesizing taurine and its expression level is high in adipose tissue. But its role in adipose tissue is poorly understood. We found that 1) The Cdo1 expression level in the mice white adipose tissue was elevated after cold exposure; 2) Knockdown of Cdo1 in C3H10T1/2 adipocytes inhibited cellular oxygen consumption, lipolysis and glucose uptake, while overexpression of Cdo1 in C3H10T1/2 adipocytes promoted cellular oxygen consumption, lipolysis and glucose uptake; 3) Adenovirus-mediated overexpression of Cdo1 in the mice inguinal subcutaneous fat enhanced thermogenesis, the expression of thermogenic genes, oxygen consumption and glucose uptake in the inguinal subcutaneous fat. In this project, by performing cellular/molecular biology experiments and by using mice models, we will investigate the role and mechanism of cysteine dioxygenase 1 (Cdo1) in regulating the browning of white adipose tissue. This study may provide new insights into the regulatory networks of white adipose tissue browning and offer potential new targets for anti-obesity strategies.