Quantifying phenotypic flexibility as the response to a high-fat challenge test in different states of metabolic health

Quantifying phenotypic flexibility as the response to a high-fat challenge test in different states of metabolic health
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DOI:
10.1096/fj.14-269852
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发表时间:
2015-11-01
期刊:
影响因子:
4.8
通讯作者:
Wopereis, Suzan
Wopereis, Suzan
中科院分区:
生物学2区
文献类型:
--
作者:
Kardinaal, Alwine F. M.;van Erk, Marjan J.;Wopereis, Suzan

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代谢在慢性高热量条件下保持体内平衡,激活餐后反应机制,这是以适应过程为代价的,例如能量储存,最终会对健康产生负面影响。本研究通过研究挑战反应曲线来量化代谢适应能力。在高脂挑战后,在3个代谢健康阶段之间比较了61个与脂肪组织质量和功能、全身应激、代谢灵活性、血管健康和葡萄糖代谢相关的生物标志物的8小时响应曲线:10名健康男性,在4周高脂、高热量饮食(额外1300千卡/天)之前和之后,以及9名代谢综合征(MetS)男性。代谢综合征受试者的空腹生物标志物浓度增加,代表3个核心过程,葡萄糖,TG和炎症控制,大多数生物标志物的挑战反应曲线发生改变。经过4周的高热量饮食干预后,与健康受试者干预前的状态相比,这3个过程没有改变,而几乎所有调节这些核心过程的内分泌、代谢和炎症过程的挑战反应曲线都发生了改变,这表明主要的分子生理学努力是为了维持稳态。因此,这项研究表明,挑战反应的变化是比空腹浓度变化更敏感的代谢弹性生物标志物。
Metabolism maintains homeostasis at chronic hypercaloric conditions, activating postprandial response mechanisms, which come at the cost of adaptation processes such as energy storage, eventually with negative health consequences. This study quantified the metabolic adaptation capacity by studying challenge response curves. After a high-fat challenge, the 8 h response curves of 61 biomarkers related to adipose tissue mass and function, systemic stress, metabolic flexibility, vascular health, and glucose metabolism was compared between 3 metabolic health stages: 10 healthy men, before and after 4 wk of highfat, high-calorie diet (1300 kcal/d extra), and 9 men with metabolic syndrome (MetS). The MetS subjects had increased fasting concentrations of biomarkers representing the 3 core processes, glucose, TG, and inflammation control, and the challenge response curves ofmost biomarkers were altered. After the 4 wk hypercaloric dietary intervention, these 3 processes were not changed, as compared with the preintervention state in the healthy subjects, whereas the challenge response curves of almost all endocrine, metabolic, and inflammatory processes regulating these core processes were altered, demonstrating major molecular physiologic efforts tomaintain homeostasis. This study thus demonstrates that change in challenge response is a more sensitive biomarker of metabolic resilience than are changes in fasting concentrations.