| Literature DB >> 30842678 |
Olof S Dallner1, Jill M Marinis2, Yi-Hsueh Lu1, Kivanc Birsoy3, Emory Werner1, Gulya Fayzikhodjaeva1, Brian D Dill4, Henrik Molina4, Arden Moscati5, Zoltán Kutalik6,7, Pedro Marques-Vidal8, Tuomas O Kilpeläinen9, Niels Grarup9, Allan Linneberg10,11,12, Yinxin Zhang1, Roger Vaughan13, Ruth J F Loos5,14, Mitchell A Lazar2, Jeffrey M Friedman15,16.
Abstract
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 elucidating the pathogenic mechanism in the subset of obese patients with low endogenous leptin levels.Entities:
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Year: 2019 PMID： 30842678 DOI： 10.1038/s41591-019-0370-1
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440