Laboratory of Genetic Metabolic Diseases, Academic Medical Center, AZ Amsterdam, Netherlands.
Amsterdam Gastroenterology and Metabolism, Academic Medical Center, AZ Amsterdam, Netherlands.
Endocr Rev. 2018 Aug 1;39(4):489-517. doi: 10.1210/er.2017-00211.
The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage, and utilization, dependent on availability and requirement, is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy homeostasis in times of either caloric excess or caloric restriction, and in times of either low or high energy demand, such as during exercise. The liver, adipose tissue, and muscle govern systemic metabolic flexibility and manage nutrient sensing, uptake, transport, storage, and expenditure by communication via endocrine cues. At a molecular level, metabolic flexibility relies on the configuration of metabolic pathways, which are regulated by key metabolic enzymes and transcription factors, many of which interact closely with the mitochondria. Disrupted metabolic flexibility, or metabolic inflexibility, however, is associated with many pathological conditions including metabolic syndrome, type 2 diabetes mellitus, and cancer. Multiple factors such as dietary composition and feeding frequency, exercise training, and use of pharmacological compounds, influence metabolic flexibility and will be discussed here. Last, we outline important advances in metabolic flexibility research and discuss medical horizons and translational aspects.
通过底物感应、运输、储存和利用的效率来适应代谢的能力，取决于可用性和需求，这被称为代谢灵活性。在这篇综述中，我们讨论了代谢灵活性的广度和深度，以及它对健康和疾病的影响。代谢灵活性对于在热量过剩或热量限制时，以及在低能量需求或高能量需求时（如运动时）维持能量平衡至关重要。肝脏、脂肪组织和肌肉通过内分泌信号进行通讯，调节全身代谢灵活性，并管理营养感应、摄取、运输、储存和消耗。在分子水平上，代谢灵活性依赖于代谢途径的配置，这些途径受关键代谢酶和转录因子的调节，其中许多与线粒体密切相互作用。然而，代谢灵活性的破坏或代谢不灵活性与许多病理状况有关，包括代谢综合征、2 型糖尿病和癌症。多种因素，如饮食成分和喂养频率、运动训练以及使用药物化合物，都会影响代谢灵活性，本文将对此进行讨论。最后，我们概述了代谢灵活性研究的重要进展，并讨论了医学前景和转化方面。
