Translational Research Institute for Metabolism and Diabetes, Florida Hospital, 301 E Princeton Street, Orlando, FL, 32804, USA.
Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USA.
Diabetologia. 2017 Dec;60(12):2329-2336. doi: 10.1007/s00125-017-4461-6. Epub 2017 Oct 14.
The overall beneficial effects of exercise are well studied, but why some people do not respond favourably to exercise is less understood. The National Institutes of Health Common Fund has recently launched the large-scale discovery project 'Molecular Transducers of Physical Activity in Humans' to examine the physiological and molecular (i.e. genetic, epigenetic, lipidomic, metabolomic, proteomic, etc.) responses to exercise training. A nationwide, multicentre clinical trial such as this one also provides a unique opportunity to robustly investigate the non-response to exercise in thousands of individuals that have undergone supervised aerobic- and resistance-based exercise training interventions. The term 'non-responder' is used here to address the lack of a response (to an exercise intervention) in an outcome specified a priori. Cardiorespiratory fitness ([Formula: see text]) as an exercise response variable was recently reviewed; thus, this review focuses on metabolic aspects of the non-response to exercise training. Integrated -omics platforms are discussed as an approach to disentangle the complicated relationships between endogenous and exogenous factors that drive the lack of a response to exercise in some individuals. Harnessing the power of combined -omics platforms with deep clinical phenotyping of human study participants will advance the field of exercise metabolism and shift the paradigm, allowing exercise interventions to be targeted at those most likely to benefit and identifying novel approaches to treat those who do not.
运动的整体有益效果已经得到了充分的研究，但为什么有些人对运动的反应不佳，这一点了解得还不够。美国国立卫生研究院共同基金最近启动了大规模的发现项目“人类体力活动的分子转导器”，以研究运动训练对生理和分子（即遗传、表观遗传、脂质组学、代谢组学、蛋白质组学等）的反应。这样的全国性、多中心临床试验也为在经过监督的有氧和抗阻运动训练干预下的数千名个体中，对运动的非反应进行强有力的研究提供了独特的机会。这里使用“无反应者”一词是为了说明在预先指定的结果中缺乏反应（对运动干预的反应）。心肺适能([Formula: see text])作为运动反应变量最近进行了综述；因此，本综述侧重于运动训练无反应的代谢方面。本文讨论了整合组学平台作为一种方法，以厘清导致某些个体对运动无反应的内源性和外源性因素之间复杂关系。利用组合组学平台的强大功能，并对人类研究参与者进行深入的临床表型分析，将推动运动代谢领域的发展，并改变范式，使运动干预能够针对最有可能受益的人群，并为那些没有受益的人群寻找新的治疗方法。
