Morita Sumiyo, Nakabayashi Kazuhiko, Kawai Tomoko, Hayashi Keiko, Horii Takuro, Kimura Mika, Kamei Yasutomi, Ogawa Yoshihiro, Hata Kenichiro, Hatada Izuho
Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi Maebashi, 371-8512, Japan.
Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, 2-10-1 Okura Setagaya-ku Tokyo, 157-8535, Japan.
Sci Rep. 2016 Feb 12;6:21693. doi: 10.1038/srep21693.
Previously, we found that C57BL/6J (B6) mice are more prone to develop obesity than PWK mice. In addition, we analyzed reciprocal crosses between these mice and found that (PWK × B6) F1 mice, which have B6 fathers, are more likely to develop dietary obesity than (B6 × PWK) F1 mice, which have B6 mothers. These results suggested that diet-induced obesity is paternally transmitted. In this study, we performed transcriptome analysis of adipose tissues of B6, PWK, (PWK × B6) F1, and (B6 × PWK) F1 mice using next-generation sequencing. We found that paternal transmission of diet-induced obesity was correlated with genes involved in adipose tissue inflammation, metal ion transport, and cilia. Furthermore, we analyzed the imprinted genes expressed in white adipose tissue (WAT) and obesity. Expression of paternally expressed imprinted genes (PEGs) was negatively correlated with body weight, whereas expression of maternally expressed imprinted genes (MEGs) was positively correlated. In the obesity-prone B6 mice, expression of PEGs was down-regulated by a high-fat diet, suggesting that abnormally low expression of PEGs contributes to high-fat diet-induced obesity in B6 mice. In addition, using single-nucleotide polymorphisms that differ between B6 and PWK, we identified candidate imprinted genes in WAT.
此前，我们发现C57BL/6J（B6）小鼠比PWK小鼠更容易发生肥胖。此外，我们分析了这两种小鼠之间的 reciprocal crosses，发现具有B6父亲的（PWK×B6）F1小鼠比具有B6母亲的（B6×PWK）F1小鼠更易发生饮食性肥胖。这些结果表明饮食诱导的肥胖是父系遗传的。在本研究中，我们使用下一代测序技术对B6、PWK、（PWK×B6）F1和（B6×PWK）F1小鼠的脂肪组织进行了转录组分析。我们发现饮食诱导肥胖的父系遗传与参与脂肪组织炎症、金属离子转运和纤毛的基因相关。此外，我们分析了在白色脂肪组织（WAT）中表达的印记基因与肥胖的关系。父系表达的印记基因（PEGs）的表达与体重呈负相关，而母系表达的印记基因（MEGs）的表达与体重呈正相关。在易肥胖的B6小鼠中，高脂饮食下调了PEGs的表达，提示PEGs的异常低表达促成了B6小鼠的高脂饮食诱导肥胖。此外，利用B6和PWK之间不同的单核苷酸多态性，我们在WAT中鉴定了候选印记基因。
