Data_Sheet_3_A Constraint-Based Model Analysis of Enterocyte Mitochondrial Adaptation to Dietary Interventions of Lipid Type and Lipid Load.XLSX

Computational modeling of mitochondrial adaptability and flexibility in the small intestine upon different nutritional exposures will provide insights that will help to define healthy diet interventions. Therefore, a murine enterocyte-specific mitochondrial constraint-based metabolic model (named MT_mmuENT127) was constructed and used to simulate mitochondrial behavior under different dietary conditions, representing various levels and composition of nutrients absorbed by the enterocytes in mice, primarily focusing on metabolic pathways. Our simulations predicted that increasing the fraction of marine fatty acids in the diet, or increasing the dietary lipid/carbohydrate ratio resulted in (i) an increase in mitochondrial fatty acid beta oxidation, and (ii) changes in only a limited subset of mitochondrial reactions, which appeared to be independent of gene expression regulation. Moreover, transcript levels of mitochondrial proteins suggested unaltered fusion–fission dynamics by an increased lipid/carbohydrates ratio or by increased fractions of marine fatty acids. In conclusion, our enterocytic mitochondrial constraint-based model was shown to be a suitable platform to investigate effects of dietary interventions on mitochondrial adaptation and provided novel and deeper insights in mitochondrial metabolism and regulation.

针对不同营养暴露条件下小肠线粒体适应性与灵活性的计算建模研究，将为明确健康饮食干预方案提供重要见解。因此，本研究构建了小鼠肠上皮细胞特异性线粒体约束性代谢模型（constraint-based metabolic model，命名为MT_mmuENT127），并利用该模型模拟不同膳食条件下的线粒体行为——此类膳食条件对应小鼠肠上皮细胞吸收的不同水平与组成的营养物质，研究主要聚焦于代谢通路。模拟结果预测，膳食中海洋源性脂肪酸占比提升，或膳食脂类/碳水化合物比值升高，将带来两方面变化：其一，线粒体脂肪酸β氧化水平上升；其二，仅有限的线粒体反应子集发生改变，且此类改变似乎不受基因表达调控的影响。此外，线粒体蛋白的转录水平分析显示，膳食脂类/碳水化合物比值升高或海洋源性脂肪酸占比提升，并未改变线粒体融合-分裂动力学状态。综上，本研究所构建的肠上皮细胞线粒体约束性代谢模型，是探究饮食干预对线粒体适应性影响的合适平台，并为线粒体代谢与调控机制提供了全新且更深入的见解。