作者
Olof S Dallner, Jill M Marinis, Yi-Hsueh Lu, Kivanc Birsoy, Emory Werner, Gulya Fayzikhodjaeva, Brian D Dill, Henrik Molina, Arden Moscati, Zoltán Kutalik, Pedro Marques-Vidal, Tuomas O Kilpeläinen, Niels Grarup, Allan Linneberg, Yinxin Zhang, Roger Vaughan, Ruth JF Loos, Mitchell A Lazar, Jeffrey M Friedman
发表日期
2019/3
期刊
Nature medicine
卷号
25
期号
3
页码范围
507-516
出版商
Nature Publishing Group US
简介
Quantitative changes in leptin concentration lead to alterations in food intake and body weight, but the regulatory mechanisms that control leptin gene expression are poorly understood. Here we report that fat-specific and quantitative leptin expression is controlled by redundant cis elements and trans factors interacting with the proximal promoter together with a long noncoding RNA (lncOb). Diet-induced obese mice lacking lncOb show increased fat mass with reduced plasma leptin levels and lose weight after leptin treatment, whereas control mice do not. Consistent with this finding, large-scale genetic studies of humans reveal a significant association of single-nucleotide polymorphisms (SNPs) in the region of human lncOb with lower plasma leptin levels and obesity. These results show that reduced leptin gene expression can lead to a hypoleptinemic, leptin-responsive form of obesity and provide a framework for …
学术搜索中的文章
OS Dallner, JM Marinis, YH Lu, K Birsoy, E Werner… - Nature medicine, 2019