Horikawa Makoto, Nomura Toshihisa, Hashimoto Teppei, Sakamoto Kazuichi
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
J Biochem. 2008 Aug;144(2):149-58. doi: 10.1093/jb/mvn055. Epub 2008 Apr 19.
Recently, it was reported that a deficit in the mouse stearoyl-CoA desaturase 1 gene decreases biosynthesis and accumulation of fatty acid and revitalizes the beta-oxidation of fatty acid. To examine the physiological role of fatty acid desaturase (FAT) and elongase (ELO)-gene transduction in ontogeny, fatty acid accumulation and individual lifespan, we performed bacteria-mediated RNA interference (RNAi) in the nematode Caenorhabditis elegans. Suppression of the expression of FAT-2 gene mRNA caused a drastic decrease in the amount of body fat and defects in egg-hatching. The amount of body fat was markedly decreased, and body size reduced, by down regulation of FAT-6 and FAT-7, whereas lifespan was drastically reduced. RNAi of the FAT-2 gene caused a remarkable increase of the beta-oxidation-related gene expression and the DAF-16 transcriptional activity, whereas, ELO-2 RNAi caused a remarkable decrease in fatty acid biosynthesis-related gene expression. Additionally, RNAi of FAT-6 decreased the mRNA levels of the genes involved in fatty acid synthesis, and FAT-7 RNAi increased the mRNA levels of beta-oxidation system genes. These results indicated that the elongation and desaturation of fatty acids are integral to various phenomena such as ontogeny and lifespan and play important roles in fatty acid accumulation and consumption.
最近有报道称,小鼠硬脂酰辅酶A去饱和酶1基因的缺陷会减少脂肪酸的生物合成和积累,并使脂肪酸的β-氧化恢复活力。为了研究脂肪酸去饱和酶(FAT)和延长酶(ELO)基因转导在个体发育、脂肪酸积累和个体寿命中的生理作用,我们在线虫秀丽隐杆线虫中进行了细菌介导的RNA干扰(RNAi)。FAT-2基因mRNA表达的抑制导致体内脂肪量急剧减少和孵化缺陷。通过下调FAT-6和FAT-7,体内脂肪量显著减少,体型减小,而寿命则急剧缩短。FAT-2基因的RNA干扰导致β-氧化相关基因表达和DAF-16转录活性显著增加,而ELO-2 RNA干扰导致脂肪酸生物合成相关基因表达显著降低。此外,FAT-6的RNA干扰降低了参与脂肪酸合成的基因的mRNA水平,FAT-7 RNA干扰增加了β-氧化系统基因的mRNA水平。这些结果表明,脂肪酸的延长和去饱和对于个体发育和寿命等各种现象不可或缺,并且在脂肪酸积累和消耗中发挥重要作用。