Systems Biology Will Direct Vascular-Targeted Therapy for Obesity
Systems Biology Will Direct Vascular-Targeted Therapy for Obesity
复制标题
系统生物学将指导肥胖症的血管靶向治疗
DOI：
10.3389/fphys.2020.00831
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发表时间：
2020-07-15
影响因子：
4
通讯作者：
Imoukhuede, P. I.
中科院分区：
文献类型：
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作者：
Fang, Yingye;Kaszuba, Tomasz;Imoukhuede, P. I.
体重增加期间健康的脂肪组织扩张和代谢需要协调的血管生成和淋巴管生成。这些血管生长过程依赖于血管内皮生长因子（VEGF）家族的配体和受体（VEGFRs）。几项研究表明，通过调节VEGF：VEGFR信号传导来控制血管生长可有益于治疗肥胖症;然而，失调的血管生成和淋巴管生成与几种慢性组织炎症症状相关，包括缺氧、免疫细胞积聚和纤维化，导致肥胖症相关的代谢紊乱。理想的肥胖治疗应该最大限度地减少脂肪组织扩张和不良代谢后果的出现，这可以通过使VEGF：VEGFR信号正常化来实现。为了实现这一目标，有必要对肥胖症中血管和代谢系统的相互依赖性进行系统研究，并使用工具预测个性化治疗范围，以通过血管靶向治疗改善患者结局。系统生物学可以确定关键的VEGF：VEGFR信号传导机制，可以有针对性地使脂肪组织扩张消退，并可以预测不同血管靶向方法的代谢后果。建立一个预测性的、生物学上忠实的平台需要适当的计算模型和定量的组织特异性数据。在这里，我们讨论了血管内皮生长因子：血管内皮生长因子受体信号在血管生成，淋巴管生成，脂肪形成，巨噬细胞的规范-调节脂肪组织扩张和代谢的关键机制的参与。然后，我们提供了有用的计算方法来模拟这些机制，并详细的定量技术获取组织特异性参数。通过计算模型和定量数据，系统生物学将能够准确表示肥胖脂肪组织，可用于指导肥胖和相关代谢紊乱的血管靶向治疗的发展。
Healthy adipose tissue expansion and metabolism during weight gain require coordinated angiogenesis and lymphangiogenesis. These vascular growth processes rely on the vascular endothelial growth factor (VEGF) family of ligands and receptors (VEGFRs). Several studies have shown that controlling vascular growth by regulating VEGF:VEGFR signaling can be beneficial for treating obesity; however, dysregulated angiogenesis and lymphangiogenesis are associated with several chronic tissue inflammation symptoms, including hypoxia, immune cell accumulation, and fibrosis, leading to obesity-related metabolic disorders. An ideal obesity treatment should minimize adipose tissue expansion and the advent of adverse metabolic consequences, which could be achieved by normalizing VEGF:VEGFR signaling. Toward this goal, a systematic investigation of the interdependency of vascular and metabolic systems in obesity and tools to predict personalized treatment ranges are necessary to improve patient outcomes through vascular-targeted therapies. Systems biology can identify the critical VEGF:VEGFR signaling mechanisms that can be targeted to regress adipose tissue expansion and can predict the metabolic consequences of different vascular-targeted approaches. Establishing a predictive, biologically faithful platform requires appropriate computational models and quantitative tissue-specific data. Here, we discuss the involvement of VEGF:VEGFR signaling in angiogenesis, lymphangiogenesis, adipogenesis, and macrophage specification - key mechanisms that regulate adipose tissue expansion and metabolism. We then provide useful computational approaches for simulating these mechanisms, and detail quantitative techniques for acquiring tissue-specific parameters. Systems biology, through computational models and quantitative data, will enable an accurate representation of obese adipose tissue that can be used to direct the development of vascular-targeted therapies for obesity and associated metabolic disorders.