Nutrition, Metabolism & Genomics Group, Division of Human Nutrition, Wageningen University, Stippeneng 4, Wageningen, 6708 WE, The Netherlands.
Laboratory of Systems and Synthetic Biology, Wageningen University, Stippeneng 4, Wageningen, 6708 WE, The Netherlands.
Sci Rep. 2017 Aug 18;7(1):8784. doi: 10.1038/s41598-017-07350-1.
The small intestine serves as gatekeeper at the interface between body and diet and is thought to play an important role in the etiology of obesity and associated metabolic disorders. A computational modelling approach was used to improve our understanding of the metabolic responses of epithelial cells to different diets. A constraint based, mouse-specific enterocyte metabolic model (named mmu_ENT717) was constructed to describe the impact of four fully characterized semi-purified diets, that differed in lipid and carbohydrate composition, on uptake, metabolism, as well as secretion of carbohydrates and lipids. Our simulation results predicted luminal sodium as a limiting factor for active glucose absorption; necessity of apical localization of glucose transporter GLUT2 for absorption of all glucose in the postprandial state; potential for gluconeogenesis in enterocytes; and the requirement of oxygen for the formation of endogenous cholesterol needed for chylomicron formation under luminal cholesterol-free conditions. In addition, for a number of enzymopathies related to intestinal carbohydrate and lipid metabolism it was found that their effects might be ameliorated through dietary interventions. In conclusion, our improved enterocyte-specific model was shown to be a suitable platform to study effects of dietary interventions on enterocyte metabolism, and provided novel and deeper insights into enterocyte metabolism.
小肠作为人体与饮食之间的界面守门员，被认为在肥胖症和相关代谢紊乱的发病机制中起着重要作用。采用计算建模方法来提高我们对上皮细胞对不同饮食的代谢反应的理解。构建了一个基于约束的、具有小鼠特异性的肠细胞代谢模型（命名为 mmu_ENT717），用于描述四种完全特征化的半纯化饮食（在脂质和碳水化合物组成上存在差异）对碳水化合物和脂质摄取、代谢以及分泌的影响。我们的模拟结果预测，腔内腔钠离子是主动葡萄糖吸收的限制因素；在餐后状态吸收所有葡萄糖需要葡萄糖转运蛋白 GLUT2 定位于顶端；肠细胞中存在糖异生的潜力；以及在腔内腔无胆固醇条件下，形成乳糜微粒所需的内源性胆固醇的形成需要氧气。此外，对于一些与肠道碳水化合物和脂质代谢相关的酶病，发现通过饮食干预可能会减轻其影响。总之，我们改进的肠细胞特异性模型被证明是研究饮食干预对肠细胞代谢影响的合适平台，并为肠细胞代谢提供了新的、更深入的见解。
