Tareen Samar H K, Kutmon Martina, Adriaens Michiel E, Mariman Edwin C M, de Kok Theo M, Arts Ilja C W, Evelo Chris T
1Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, the Netherlands.
2Department of Bioinformatics - BiGCaT, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
Genes Nutr. 2018 Jul 5;13:17. doi: 10.1186/s12263-018-0609-3. eCollection 2018.
Metabolic flexibility is the ability of cells to change substrates for energy production based on the nutrient availability and energy requirement. It has been shown that metabolic flexibility is impaired in obesity and chronic diseases such as type 2 diabetes mellitus, cardiovascular diseases, and metabolic syndrome, although, whether it is a cause or an effect of these conditions remains to be elucidated.
In this paper, we have reviewed the literature on metabolic flexibility and curated pathways and processes resulting in a network resource to investigate the interplay between these processes in the subcutaneous adipose tissue. The adipose tissue has been shown to be responsible, not only for energy storage but also for maintaining energy homeostasis through oxidation of glucose and fatty acids. We highlight the role of pyruvate dehydrogenase complex-pyruvate dehydrogenase kinase () interaction as a regulatory switch which is primarily responsible for changing substrates in energy metabolism from glucose to fatty acids and back. Baseline gene expression of the subcutaneous adipose tissue, along with a publicly available obesity data set, are visualised on the cellular network of metabolic flexibility to highlight the genes that are expressed and which are differentially affected in obesity.
We have constructed an abstracted network covering glucose and fatty acid oxidation, as well as the regulatory switch. In addition, we have shown how the network can be used for data visualisation and as a resource for follow-up studies.
代谢灵活性是细胞根据营养物质的可利用性和能量需求改变能量产生底物的能力。研究表明,肥胖以及2型糖尿病、心血管疾病和代谢综合征等慢性疾病中代谢灵活性受损,不过,这是这些疾病的原因还是结果仍有待阐明。
在本文中,我们回顾了关于代谢灵活性以及相关途径和过程的文献,构建了一个网络资源,以研究皮下脂肪组织中这些过程之间的相互作用。脂肪组织不仅负责能量储存,还通过葡萄糖和脂肪酸的氧化来维持能量稳态。我们强调丙酮酸脱氢酶复合体 - 丙酮酸脱氢酶激酶()相互作用作为一种调节开关的作用,它主要负责能量代谢中底物从葡萄糖转变为脂肪酸以及再转变回葡萄糖的过程。皮下脂肪组织的基线基因表达以及一个公开的肥胖数据集在代谢灵活性的细胞网络上进行可视化展示,以突出肥胖中表达的基因以及受不同影响的基因。
我们构建了一个涵盖葡萄糖和脂肪酸氧化以及调节开关的抽象网络。此外,我们展示了该网络如何用于数据可视化以及作为后续研究的资源。