Imanikia Soudabeh, Hylands Peter, Stürzenbaum Stephen R
Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.
Analytical and Environmental Sciences Division, Faculty of Life Sciences & Medicine, King's College London, London, UK.
Biochem Biophys Rep. 2015 Jun 25;2:172-178. doi: 10.1016/j.bbrep.2015.06.007. eCollection 2015 Jul.
An imbalance between energy uptake and energy expenditure can lead to obesity and increase the risk of coronary heart disease, high blood pressure, stroke, type II diabetes and some cancers. Given that key elements of the energy pathway are evolutionary conserved, invertebrate research is an attractive alternative that overcomes the many legislative, financial and experimental hurdles typical of research with higher metazoan animals. Recent studies have suggested that some members of the cytochrome P450 superfamily are involved in lipid metabolism in addition to the traditional xenobiotic activity. To investigate this notion in more detail, the present study aimed to pinpoint phenotypic, genetic and genomic-level responses of using selected deletion mutants including (a member of the Δ9 desaturases) and (a member of the cytochrome P450 family). The creation of a mutant uncovered that the deletion of both genes resulted in a strain which is marked by an extended lifespan. Furthermore, it diminished the overall level of Nile Red positive compartments, which is indicative of a change in lipid metabolism. Comprehensive transcriptomics revealed that several genes involved in aging and lipid transport/homeostasis were modulated following the double deletion of and . Taken together, the results suggest the presence of a putative correlation between longevity and lipid regulation and given that both genes have human homologs, this finding may offer a new lead to investigate in higher organisms.
能量摄取与能量消耗之间的失衡会导致肥胖，并增加患冠心病、高血压、中风、II型糖尿病和某些癌症的风险。鉴于能量代谢途径的关键要素在进化过程中是保守的，无脊椎动物研究是一种有吸引力的替代方法，它克服了高等后生动物研究中常见的许多立法、资金和实验障碍。最近的研究表明，细胞色素P450超家族的一些成员除了具有传统的外源性物质代谢活性外，还参与脂质代谢。为了更详细地研究这一概念，本研究旨在确定使用选定的缺失突变体（包括Δ9去饱和酶的一个成员和细胞色素P450家族的一个成员）后的表型、遗传和基因组水平的反应。创建一个突变体发现，两个基因的缺失导致了一个寿命延长的菌株。此外，它降低了尼罗红阳性区室的总体水平，这表明脂质代谢发生了变化。综合转录组学显示，在和双缺失后，几个与衰老和脂质转运/稳态相关的基因受到了调控。综上所述，结果表明长寿与脂质调节之间可能存在相关性，鉴于这两个基因都有人类同源物，这一发现可能为在高等生物中进行研究提供新的线索。
