Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 Jiao-Chang Dong Road, Kunming, Yunnan 650223, China.
BMC Genomics. 2013 Mar 12;14:164. doi: 10.1186/1471-2164-14-164.
Animal models are indispensable to understand the lipid metabolism and lipid metabolic diseases. Over the last decade, the nematode Caenorhabditis elegans has become a popular animal model for exploring the regulation of lipid metabolism, obesity, and obese-related diseases. However, the genomic and functional conservation of lipid metabolism from C. elegans to humans remains unknown. In the present study, we systematically analyzed genes involved in lipid metabolism in the C. elegans genome using comparative genomics.
We built a database containing 471 lipid genes from the C. elegans genome, and then assigned most of lipid genes into 16 different lipid metabolic pathways that were integrated into a network. Over 70% of C. elegans lipid genes have human orthologs, with 237 of 471 C. elegans lipid genes being conserved in humans, mice, rats, and Drosophila, of which 71 genes are specifically related to human metabolic diseases. Moreover, RNA-mediated interference (RNAi) was used to disrupt the expression of 356 of 471 lipid genes with available RNAi clones. We found that 21 genes strongly affect fat storage, development, reproduction, and other visible phenotypes, 6 of which have not previously been implicated in the regulation of fat metabolism and other phenotypes.
This study provides the first systematic genomic insight into lipid metabolism in C. elegans, supporting the use of C. elegans as an increasingly prominent model in the study of metabolic diseases.
动物模型对于理解脂质代谢和脂质代谢疾病是不可或缺的。在过去的十年中,秀丽隐杆线虫已成为探索脂质代谢、肥胖和肥胖相关疾病调节的一种流行的动物模型。然而,从秀丽隐杆线虫到人类的脂质代谢的基因组和功能保守性仍不清楚。在本研究中,我们使用比较基因组学系统地分析了秀丽隐杆线虫基因组中与脂质代谢相关的基因。
我们构建了一个包含 471 个秀丽隐杆线虫脂质基因的数据库,然后将大多数脂质基因分配到 16 个不同的脂质代谢途径中,这些途径整合到一个网络中。超过 70%的秀丽隐杆线虫脂质基因具有人类同源物,在 471 个秀丽隐杆线虫脂质基因中有 237 个在人类、小鼠、大鼠和果蝇中保守,其中 71 个基因与人类代谢疾病特别相关。此外,使用 RNA 干扰(RNAi)技术破坏了 356 个具有可用 RNAi 克隆的 471 个脂质基因的表达。我们发现 21 个基因强烈影响脂肪储存、发育、繁殖和其他可见表型,其中 6 个基因以前没有被涉及到脂肪代谢和其他表型的调节。
本研究首次提供了秀丽隐杆线虫脂质代谢的系统基因组见解,支持秀丽隐杆线虫作为代谢疾病研究中日益突出的模型的使用。