以往研究发现雄激素在肥胖少年血液中的含量明显高于正常少年，但其在少年肥胖发生中的作用还尚未清楚。申请人利用自己构建的可定量研究白色脂肪细胞褐色化的小鼠模型进行小分子筛选时发现雄激素显著下调白色脂肪细胞褐色化，而白色脂肪细胞褐色化的增强能够抑制肥胖发生。申请人进一步研究发现雄激素受体的敲除消除了雄激素对白色脂肪细胞褐色化的抑制作用。此外，雄激素受体脂肪组织特异性敲除小鼠在早期表现出更多的白色脂肪细胞褐色化并且体重低于对照小鼠。通过雄激素受体的染色质免疫共沉淀等实验发现雄激素负调控褐色化关键因子Prdm16的表达。因此申请人推测雄激素的升高，激活雄激素受体，通过调控Prdm16信号途径抑制白色脂肪细胞褐色化并减少机体能量消耗，最终导致肥胖发生。申请人后续拟通过基因敲除和免疫共沉淀等实验来解析雄激素调控白色脂肪细胞褐色化的分子机制。本项研究将为治疗和预防机体少年期肥胖提供新的治疗靶点和理论依据。

Previous studies have showed that the content of androgen in the blood of obese adolescents is significantly higher than normal adolescents, but its role in the occurrence of juvenile obesity is still not clear. Applicants found that androgen significantly down-regulated the browning of white adipocytes by their own mouse model that can quantitatively study the white adipocyte browning through small molecule screening, and the enhancement of browning of white adipocytes could prevent the occurrence of obesity. Applicants have further studied that knockdown of the androgen receptor eliminates the inhibitory effect of androgens on the browning of white adipocytes. In addition, adipose tissue-specific androgen receptor knockout mice showed more white adipocyte browning and less body weight than control mice at an early stage. The chromatin immunoprecipitation of androgen receptor showed that the expression of Prdm16, a key factor in white adipocyte browning, was negatively regulated by androgen. Therefore, the applicant speculates that the increase of androgen, activates the androgen receptor, inhibits the browning of white adipocytes by regulating the Prdm16 signaling pathway, reduces the energy consumption and ultimately leads to obesity. The applicants intend to interpret the molecular mechanism of androgen to regulate white adipocyte browning. This study will provide new therapeutic targets and theoretical basis for the treatment and prevention of juvenile obesity.