動物模型對研究脂代謝調(diào)控和代謝性疾病是必不可少的,。模式生物秀麗線蟲（Caenorhabditis elegans）是第一個全基因組被測序的真核生物（1998年）,。
在過去的10多年中,，由于其生活周期短、低成本,、易培養(yǎng)和操作等優(yōu)點,，秀麗線蟲成為一個研究脂代謝調(diào)控,、肥胖和肥胖相關(guān)代謝性疾病發(fā)病機理的良好模式動物,。然而,，至今為止，我們不清楚,，秀麗線蟲基因組中有多少編碼脂代謝酶的基因和參與的代謝途徑,，以及它們在果蠅、小鼠,、大鼠和人中的保守性等,。
梁斌課題組張玉茹博士等人研究秀麗線蟲基因組發(fā)現(xiàn)，秀麗線蟲21000個左右的基因中,，至少有471個基因是編碼脂代謝酶的基因,，參與16條不同脂類的代謝途徑。由此,，他們構(gòu)建了第一個秀麗線蟲脂代謝基因數(shù)據(jù)庫,，繪制了第一張秀麗線蟲脂代謝途徑網(wǎng)絡(luò)圖,。
同時，通過比較基因組學(xué)方法,，他們進一步從人、小鼠,、大鼠和果蠅基因組中分別發(fā)掘到581,、585、563和428個脂代謝基因,，其中,，237個脂代謝基因在5個物種中都具有，70%以上的秀麗線蟲脂代謝基因在人中是保守的,。在581個人的脂代謝基因中,，97個和代謝性疾病有關(guān)，其中有94個在秀麗線蟲基因組中存在,，表明秀麗線蟲和人的脂代謝基因高度保守,。
隨后，利用秀麗線蟲全基因組RNAi文庫的優(yōu)勢,，他們分析了356個脂代謝基因的生物學(xué)功能,，發(fā)現(xiàn)有21個基因顯著影響脂肪含量和生長發(fā)育等。該研究第一次從基因組的角度分析了秀麗線蟲脂代謝基因及其代謝途徑,，為該領(lǐng)域未來的研究提供了大量有益的資源,，同時也進一步支持秀麗線蟲是研究脂代謝和代謝性疾病的良好動物模型。
該文章于近期在線發(fā)表于BMC Genomics,。(生物谷Bioon.com)
doi:10.1186/1471-2164-14-164
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PMID:
Comparative genomics and functional study of lipid metabolic genes in Caenorhabditis elegans
Yuru Zhang, Xiaoju Zou, Yihong Ding, Haizhen Wang, Xiaoyun Wu and Bin Liang.
Background: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.
Results: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. Conclusions：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.
