The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Rovereto, Italy.
Department of Mathematics, University of Trento, Italy.
Sci Rep. 2017 Jan 23;7:41231. doi: 10.1038/srep41231.
Recent research adds to a growing body of literature on the essential role of ceramides in glucose homeostasis and insulin signaling, while the mechanistic interplay between various components of ceramide metabolism remains to be quantified. We present an extended model of C16:0 ceramide production through both the de novo synthesis and the salvage pathways. We verify our model with a combination of published models and independent experimental data. In silico experiments of the behavior of ceramide and related bioactive lipids in accordance with the observed transcriptomic changes in obese/diabetic murine macrophages at 5 and 16 weeks support the observation of insulin resistance only at the later phase. Our analysis suggests the pivotal role of ceramide synthase, serine palmitoyltransferase and dihydroceramide desaturase involved in the de novo synthesis and the salvage pathways in influencing insulin resistance versus its regulation.
最近的研究增加了越来越多的关于神经酰胺在葡萄糖稳态和胰岛素信号中的重要作用的文献，而神经酰胺代谢的各种成分之间的机制相互作用仍有待量化。我们提出了一个通过从头合成和补救途径产生 C16:0 神经酰胺的扩展模型。我们使用已发表的模型和独立的实验数据组合来验证我们的模型。根据肥胖/糖尿病小鼠巨噬细胞在 5 周和 16 周时观察到的转录组变化，对神经酰胺和相关生物活性脂质行为的计算机模拟实验支持了仅在后期观察到胰岛素抵抗的观点。我们的分析表明，从头合成和补救途径中涉及的神经酰胺合酶、丝氨酸棕榈酰转移酶和二氢神经酰胺去饱和酶在影响胰岛素抵抗及其调节方面起着关键作用。
