Henry Wellcome Centre for Gene Function, Department of Physiology, Anatomy; and Genetics, University of Oxford, Parks Road, Oxford, United Kingdom.
Medical Research Council Harwell, Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxford, United Kingdom.
PLoS One. 2014 May 19;9(5):e97162. doi: 10.1371/journal.pone.0097162. eCollection 2014.
Single nucleotide polymorphisms in the first intron of the fat-mass-and-obesity-related gene FTO are associated with increased body weight and adiposity. Increased expression of FTO is likely underlying this obesity phenotype, as mice with two additional copies of Fto (FTO-4 mice) exhibit increased adiposity and are hyperphagic. FTO is a demethylase of single stranded DNA and RNA, and one of its targets is the m6A modification in RNA, which might play a role in the regulation of gene expression. In this study, we aimed to examine the changes in gene expression that occur in FTO-4 mice in order to gain more insight into the underlying mechanisms by which FTO influences body weight and adiposity. Our results indicate an upregulation of anabolic pathways and a downregulation of catabolic pathways in FTO-4 mice. Interestingly, although genes involved in methylation were differentially regulated in skeletal muscle of FTO-4 mice, no effect of FTO overexpression on m6A methylation of total mRNA was detected.
肥胖相关基因 FTO 第一内含子的单核苷酸多态性与体重增加和肥胖有关。FTO 的表达增加可能是这种肥胖表型的基础，因为具有两个额外 Fto 拷贝的 FTO-4 小鼠表现出增加的肥胖和多食。FTO 是单链 DNA 和 RNA 的去甲基酶，其靶标之一是 RNA 中的 m6A 修饰，这可能在基因表达调控中发挥作用。在这项研究中，我们旨在研究 FTO-4 小鼠中发生的基因表达变化，以更深入地了解 FTO 影响体重和肥胖的潜在机制。我们的结果表明，FTO-4 小鼠中的合成代谢途径上调，分解代谢途径下调。有趣的是，尽管 FTO-4 小鼠骨骼肌中的甲基化相关基因存在差异调节，但未检测到 FTO 过表达对总 mRNA m6A 甲基化的影响。
