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Fat accumulation in Caenorhabditis elegans is mediated by SREBP homolog SBP-1

机译:秀丽隐杆线虫的脂肪积累是由SREBP同源物SBP-1介导的

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Research into the metabolism of fats may reveal potential targets for developing pharmaceutical approaches to obesity and related disorders. Such research may be limited, however, by the cost and time involved in using mammalian subjects or developing suitable cell lines. To determine whether invertebrates could be used to carry out such research more efficiently, we investigated the ability of Caenorhabditis elegans (C. elegans) to accumulate body fat following the consumption of excess calories and the mechanisms it uses to metabolize fat. C. elegans worms were grown on media containing various sugars and monitored for changes in body fat and expression of sbp-1, a homolog of the mammalian transcription factor SREBP-1c, which facilitates fat storage in mammals. The fat content increased markedly in worms exposed to glucose. In situ analysis of gene expression in transgenic worms carrying the GFP-labeled promoter region of sbp-1 revealed that sbp-1 mRNA was strongly expressed in the intestine. An sbp-1 knockdown caused a reduction in body size, fat storage, and egg-laying activity. RT-PCR analysis revealed a considerable decrease in the expression of fatty acid synthetic genes (including elo-2, fat-2, and fat-5) and a considerable increase of starvation-inducible gene acs-2. Normal egg-laying activity and acs-2 expression were restored on exposure to a polyunsaturated fatty acid. These findings suggest that SBP-1 and SREBP regulate the amount and composition of fat and response to starvation in a similar manner. Thus, C. elegans may be an appropriate subject for studying the metabolism of fats.
机译:对脂肪代谢的研究可能揭示开发针对肥胖症和相关疾病的药物方法的潜在目标。然而,这种研究可能受到使用哺乳动物受试者或开发合适的细胞系所涉及的成本和时间的限制。为了确定无脊椎动物是否可以用于更有效地进行此类研究,我们研究了秀丽隐杆线虫(Ca.orele elegans)在摄入过量卡路里后的体内脂肪积累能力以及其代谢脂肪的机制。秀丽隐杆线虫蠕虫在含有各种糖的培养基上生长,并监测体内脂肪的变化和sbp-1的表达,sbp-1是哺乳动物转录因子SREBP-1c的同源物,可促进哺乳动物中的脂肪储存。暴露于葡萄糖的蠕虫中的脂肪含量显着增加。原位分析携带sbp-1的GFP标记启动子区域的转基因蠕虫中的基因表达,发现sbp-1 mRNA在肠道中强烈表达。 sbp-1敲低导致体重减少,脂肪储存和产卵活性降低。 RT-PCR分析表明,脂肪酸合成基因(包括elo-2,fat-2和fat-5)的表达显着下降,而饥饿诱导基因acs-2则显着增加。暴露于多不饱和脂肪酸可恢复正常的产卵活性和acs-2表达。这些发现表明,SBP-1和SREBP以类似的方式调节脂肪的数量和组成以及对饥饿的反应。因此,秀丽隐杆线虫可能是研究脂肪代谢的合适对象。

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