Snord116 is critical in the regulation of food intake and body weight.
Snord116 is critical in the regulation of food intake and body weight.
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DOI：
10.1038/srep18614
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发表时间：
2016-01-04
影响因子：
4.6
通讯作者：
Herzog H
中科院分区：
文献类型：
--
作者：
Qi Y;Purtell L;Fu M;Lee NJ;Aepler J;Zhang L;Loh K;Enriquez RF;Baldock PA;Zolotukhin S;Campbell LV;Herzog H
Prader-Willi综合征（PWS）是人类肥胖的主要遗传原因。最近的临床报告表明，Snord 116基因簇的微缺失可导致PWS，然而，编码的snoRNA的贡献程度是未知的。在这里，我们发现全球缺乏Snord 116的小鼠出生体重低、体重增加、能量消耗和食欲过盛。与此一致，下丘脑基因表达的微阵列分析揭示了摄食相关途径的显著改变，这也通过原位杂交证实。重要的是，仅从表达NPY的神经元中选择性缺失Snord 116几乎完全模拟了整体缺失表型，包括持续的低出生体重、成年早期体重增加、能量消耗增加和食欲亢进。从机制上讲，Snord 116在NPY神经元中的缺乏导致与超噬表型一致的NPY mRNA的上调，并表明Snord 116在控制可能在PWS中失调的NPY神经元功能中的关键作用。
Prader-Willi syndrome (PWS) is the predominant genetic cause of obesity in humans. Recent clinical reports have suggested that micro-deletion of the Snord116 gene cluster can lead to PWS, however, the extent of the contributions of the encoded snoRNAs is unknown. Here we show that mice lacking Snord116 globally have low birth weight, increased body weight gain, energy expenditure and hyperphagia. Consistent with this, microarray analysis of hypothalamic gene expression revealed a significant alteration in feeding related pathways that was also confirmed by in situ hybridisation. Importantly, selective deletion of Snord116 only from NPY expressing neurons mimics almost exactly the global deletion phenotype including the persistent low birth weight, increased body weight gain in early adulthood, increased energy expenditure and hyperphagia. Mechanistically, the lack of Snord116 in NPY neurons leads to the upregulation of NPY mRNA consistent with the hyperphagic phenotype and suggests a critical role of Snord116 in the control of NPY neuronal functions that might be dysregulated in PWS.