Cui Xianwei, You Lianghui, Li Yun, Zhu Lijun, Zhang Fan, Xie Kaipeng, Cao Yan, Ji Chenbo, Guo Xirong
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
Nanjing Maternal and Child Health Medical Institute, Nanjing Medical University Affiliated Nanjing Maternal and Child Health Hospital, Nanjing, China; and.
FASEB J. 2016 Dec;30(12):4301-4312. doi: 10.1096/fj.201600694R. Epub 2016 Sep 21.
Brown adipose tissue (BAT) oxidizes fatty acids for thermogenesis and could therefore be considered as part of a new strategy in combating obesity and associated metabolic diseases. It is well established that aging is accompanied by a decline of brown adipocyte regenerative capacity. How aging contributes to this loss is poorly understood. Here, we identify a long noncoding RNA, uc.417, which is transcribed from an ultraconserved region in rodents. Expression of uc.417 increases with age. Ectopic expression of uc.417 impairs adipogenesis and the thermogenic program in brown adipocytes. However, uc.417 is not required for brown fat function. In vivo, uc.417 attenuates the cold-induced thermogenic program in mouse BAT. Moreover, we find that uc.417 moderately inhibits phosphorylation of p38MAPK without affecting the total protein level of p38MAPK. The p38MAPK pathway is essential for activating BAT to stimulate uncoupling protein 1 gene expression. The data point to uc.417 as being an important factor in an age-dependent loss of function of brown adipose tissue.-Cui, X., You, L., Li, Y., Zhu, L., Zhang, F., Xie, K., Cao, Y., Ji, C., Guo, X. A transcribed ultraconserved noncoding RNA, uc.417, serves as a negative regulator of brown adipose tissue thermogenesis.
棕色脂肪组织（BAT）通过氧化脂肪酸来产热，因此可被视为对抗肥胖及相关代谢疾病新策略的一部分。众所周知，衰老伴随着棕色脂肪细胞再生能力的下降。但衰老如何导致这种能力丧失却鲜为人知。在此，我们鉴定出一种长链非编码RNA，uc.417，它由啮齿动物的一个超保守区域转录而来。uc.417的表达随年龄增长而增加。uc.417的异位表达会损害棕色脂肪细胞的脂肪生成和产热程序。然而，棕色脂肪功能并不需要uc.417。在体内，uc.417会减弱小鼠BAT中冷诱导的产热程序。此外，我们发现uc.417适度抑制p38MAPK的磷酸化，但不影响p38MAPK的总蛋白水平。p38MAPK信号通路对于激活BAT以刺激解偶联蛋白1基因表达至关重要。这些数据表明uc.417是棕色脂肪组织功能随年龄丧失的一个重要因素。——崔X、尤L、李Y、朱L、张F、谢K、曹Y、季C、郭X。一种转录的超保守非编码RNA，uc.417，作为棕色脂肪组织产热的负调节因子。
