Abstract
The objective of the study was to assess the ranges of phenotypic flexibility as a measurement of health within the apparently healthy population. Therefore, a total of 100 healthy subjects were enrolled (50 males, 50 females) with a range in age (20-70 yrs) and in body fat percentage (low, medium, high), to ensure variation in phenotypic flexibility. Phenotypic flexibility was quantified by measuring in each volunteer the response of 160 markers to the PhenFlex challenge test (PC). The PC is a drink containing high amounts of fat and glucose. We have shown previously that this challenge test is able to quantify the adaptive capacities of most relevant metabolic processes for diet-related health. The markers were selected to monitor the response of the following 4 processes relevant for phenotypic flexibility: glucose metabolism, lipid metabolism, protein metabolism, and low grade chronic stress. The markers were measured in blood samples taken at fasting and 6 time-points (t= 0.5, 1, 2, 4, 6 and 8h) after PC. Next, the range in phenotypic flexibility of the study population was analyzed in the “health-space”, a tool developed at TNO that shows individual phenotypic flexibility in a 4 dimensional space defined by the 4 processes. The health space showed a different adaptation to PC in the extremes of the recruited population: persons of young age with low to normal fat percentage had a significant different response to PC compared to persons of old age with normal to high fat percentage (both genders). Furthermore, the health space allowed the quantification of the individual metabolic health state. Ultimately, visualizing phenotypic flexibility in the health space before and after nutritional interventions will allow the evaluation of individual efficacy of the intervention.
Highlights
A key feature of metabolic health is the ability to adapt upon dietary perturbations
Young and leaner subjects showed higher phenotypic flexibility in all health domains when compared to elderly subjects with higher adiposity To investigate if male and female subjects of higher age (60–70 years of age) and normal to high body fat percentage would respond differently to PhenFlex test” (PFT) as compared to young subjects (20–30 years of age) with low to normal body fat percentage, we used the health space methodology
As the importance further declines, features which serve as common biomarkers in type 2 diabetes mellitus (T2D) appear (4-methyl-2-oxovaleric acid, 3-methyl-2-oxovaleric acid, fasting glucose, Matsuda index, and positive area under the curve (AUC) for insulin) that all have higher concentrations in the “reduced phenotypic flexibility” group
Summary
A key feature of metabolic health is the ability to adapt upon dietary perturbations. A standardized optimal nutritional challenge test was defined after the performance of a systematic literature review [5], which was named the “PhenFlex test” (PFT) This “PhenFlex test” was characterized, van den Broek et al Genes & Nutrition (2017) 12:32 where 132 parameters were quantified during the 8-h response time course, that report on 26 metabolic processes distributed over seven organs (gut, liver, adipose, pancreas, vasculature, muscle, kidney) and systemic stress [6]. It was demonstrated that the PFT and defined new biomarkers are reliable in discriminating metabolically impaired subjects with type 2 diabetes from healthy subjects, since it was a more sensitive, early, and meaningful measure than the corresponding overnight fasting measure [6] For these reasons, the quantification of the response after a (nutritional) challenge may be a good alternative for the “classic (i.e., overnight fasting) biomarkers” in nutritional and health sciences. It is important to characterize the response to PFT in the healthy range of the population, ranging from an optimal towards a suboptimal response to the PFT as a measure of health
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
