肥胖病逐渐成为一种全球性的流行病, 伴随它产生的各种代谢综合征已严重危及人类健康。白色脂肪棕色化能显著促进机体能量的消耗，有利于预防或治疗肥胖。本课题组一直从事多功能蛋白Tudor-SN的相关研究，前期研究发现:1.Tudor-SN的缺失可以抑制脂肪细胞分化;2.Tudor-SN与成脂关键蛋白PPARγ相互作用，并促进其下游白色脂肪标志基因的转录;3.冷暴露下Tudor-SN的敲除可导致棕色脂肪标志基因和PPARγ去乙酰化酶SIRT1的表达明显增高;4.Tudor-SN可以与影响SIRT1活性的PARP-1结合。本项目我们通过构建脂肪组织特异性Tudor-SN敲除小鼠模型，利用代谢组学结合分子生物学实验，研究Tudor-SN对白色脂肪棕色化的调控作用和机制，并探讨敲除Tudor-SN对高脂诱导的肥胖是否有抵抗作用，有助于为肥胖症及其相关代谢疾病的预防和治疗提供新的治疗靶点。

The pandemic rise in the prevalence of obesity, as well as its comorbidities, such as type-2 diabetes and cardiovascular diseases, has made it imperative to develop novel anti-obesity therapeutics. The browning of white adipocytes can significantly promote the energy consumption, improve glucose and lipid metabolism．Tudor-SN protein is a highly conserved and ubiquitously expressed multifunctional protein. Previous Studies showed that 1) Tudor-SN had a positive correlation with adipogenesis, once Tudor-SN had been knocked out in MEF cells, adipogenesis can be totally inhibited; 2) Tudor-SN and PPARγ combined with each other via the SN domain of Tudor-SN. Tudor-SN could combine to PPRE region of PPARγ target genes and promote the white fat gene expression (aP2 and adipsin); 3) Under cold exposure, the deficiency of Tudor-SN led to the appearance of brown fat gene expression, including UCP1, PGC-1a, PRDM16 and FGF21, as well as SIRT1 activation; 4) Tudor-SN could combines to PARP-1. It is reported that the deletion of the PARP-1 increases NAD+ content and SIRT1 activity in brown adipose tissue. Based on our previous study, we will establish an adipose-specific Tudor-SN knock-out mouse model (Tudor-SNaP2KO). By using cell model of adipocyte differentiation and Tudor-SNaP2KO mouse model, we will further study the potential function mechanism of Tudor-SN in browning of white adipocytes and investigate whether loss-of-function of Tudor-SN is involved in resistance to dietary obesity. This finding opens a new avenue to understand the molecular control of browning of white adipocytes and it might be the therapeutic target for obesity and its related metabolic disorders.