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

Abstract

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 of most 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 to maintain homeostasis. This study thus demonstrates that change in challenge response is a more sensitive biomarker of metabolic resilience than are changes in fasting concentrations.-Kardinaal, A. F. M., van Erk, M. J., Dutman, A. E., Stroeve, J. H. M., van de Steeg, E., Bijlsma, S., Kooistra, T., van Ommen, B., Wopereis, S. Quantifying phenotypic flexibility as the response to a highfat challenge test in different states of metabolic health. FASEB J. 29, 4600-4613 (2015). www.fasebj.org

Multi-parameter comparison of a standardized mixed meal tolerance test in healthy and type 2 diabetic subjects: the PhenFlex challenge

“…The wash-out period between the two challenge tests was at least 2 days. On study days, blood samples were taken at t = 0 (≥ 10 h of fasting) and six time points (t = 0.5, t = 1, t = 2, t = 4, t = 6, and t = 8 h) after consumption of the challenge drinks for analysis of a total of 132 different metabolic markers on the results of previous studies with a similar study design [6,[19][20][21]. To minimize the risk of bias and enhance the validity of statistical comparisons, we choose to only include male subjects in this explorative study.…”

“…The use of emerging technologies like metabolic profiling and targeted proteomics in metabolic tolerance tests has allowed the development of a new generation of biomarkers [5] by the simultaneous quantification of multiple processes [3,[6][7][8][9][10][11]. The response to challenges may be used to derive biomarkers for maintenance of physiological function and ultimately as indicator for prevention of (metabolic) diseases.…”

“…There is a strongly increasing interest in this type of biomarker in nutrition and health studies, demonstrating their use in uncovering early alterations in metabolism preceeding chronic diseases [9,[11][12][13][14]. Recently, it was shown that quantification of challenge response significantly contributes to demonstrating health effects of food and nutrition in dietary intervention studies [6,7,[14][15][16][17][18]. A standardized optimal nutritional challenge test was defined after performance of a systematic literature review [3].…”

Design and implementation of a cross-sectional nutritional phenotyping study in healthy US adults

“…It represents a chronic metabolic challenge that may negatively or positively influence phenotypic flexibility. Kardinaal et al found that healthy individuals given a 4 week high-fat and highcaloric diet intervention exhibited changes in adipose tissue mass and function, metabolic flexibility (the capacity to switch between glucose and fat as fuel), vascular health, and glucose metabolism compared to the metabolic parameters collected before the high-fat and highcaloric intervention [8]. Fasting total cholesterol levels and several appetitive and metabolism-related hormones were altered in healthy subjects after consuming the high-fat and high-caloric diet, which greatly resemble the characteristics of individuals in the metabolic syndrome group.…”

“…Fasting total cholesterol levels and several appetitive and metabolism-related hormones were altered in healthy subjects after consuming the high-fat and high-caloric diet, which greatly resemble the characteristics of individuals in the metabolic syndrome group. In addition, differential responses to a high-fat challenge meal were observed in healthy subjects after the high-fat and high-caloric intervention, including postprandial biomarkers of systemic stress and inflammation, metabolic adaptation, vascular health, and glucose metabolism [8].…”