Abstract
The homeostatic challenge may provide unique opportunities for quantitative assessment of the health-promoting effects of nutritional interventions in healthy individuals. Objective. The present study is aimed at characterizing and validating the use of acute aerobic exercise (AAE) on a treadmill at 60% of VO2max for 30 min, in assessing the antioxidative and anti-inflammatory effects of a nutritional intervention. In a controlled, randomized, parallel trial of Korean black raspberry (KBR) (n = 24/group), fasting blood and urine samples collected before and following the AAE load at either baseline or 4-week follow-up were analyzed for biochemical markers, 1H-NMR metabolomics, and transcriptomics. The AAE was characterized using the placebo data only, and either the placebo or the treatment data were used in the validation. The AAE load generated a total of 50 correlations of 44 selected markers, based on Pearson's correlation coefficient analysis of 105 differential markers. Subsequent mapping of selected markers onto the KEGG pathway dataset showed 127 pathways relevant to the AAE load. Of these, 54 pathways involving 18 key targets were annotated to be related to oxidative stress and inflammation. The biochemical responses were amplified with the AAE load as compared to those with no load, whereas, the metabolomic and transcriptomic responses were downgraded. Furthermore, target-pathway network analysis revealed that the AAE load provided more explanations on how KBR exerted antioxidant effects in healthy subjects (29 pathways involving 12 key targets with AAE vs. 12 pathways involving 2 key targets without AAE). This study provides considerable insight into the molecular changes incurred by AAE and furthers our understanding that AAE-induced homeostatic perturbation could magnify oxidative and inflammatory responses, thereby providing a unique opportunity to test functional foods for antioxidant and anti-inflammatory purposes in clinical settings with healthy subjects.
Highlights
With people living longer, the attention toward functional foods that promote health maintenance and chronic disease prevention has increased at an alarming rate
The following linear mixed effect (LME) model analysis allowed us to identify a total of 105 differential markers that were differently changed by the acute aerobic exercise (AAE) load, including 5 biochemical markers, 11 metabolites, and 89 transcripts
We identified various AAE-induced differential molecular markers, including CAT, GSH, IL-6, lactate dehydrogenase (LDH), formate, glucose, glycerol, lysine, succinate, ABCB11, creatine kinase mitochondrial 2 (CKMT2), EREG, FBJ murine osteosarcoma viral oncogene homolog (FOS), FBJ murine osteosarcoma viral oncogene homolog B (FOSB), insulin-like growth factor 2 (IGF2), nerve growth factor receptor (NGFR), phosphodiesterase 6C (PDE6C), and WNT5A, which were implicated in 54 pathways related to oxidative and inflammatory stress
Summary
The attention toward functional foods that promote health maintenance and chronic disease prevention has increased at an alarming rate. Proving health benefits in apparently healthy individuals remains a significant bottleneck that limits the development of functional foods. Temporary and reversible perturbation of homeostasis mimics the early stage of chronic disease, leading to a significant increase in the values of response magnitudes in healthy subjects [3]. The most well-known example is the oral glucose load, which has long been applied to determine the effectiveness of nutritional interventions for improving glucose and insulin metabolism. Recent liquid chromatography-mass spectrometry studies have added other detailed scientific information by characterizing the specific metabolic changes occurring in healthy subjects receiving an oral glucose load [4, 5]. A comprehensive understanding of how AAE affects physiological processes related to oxidation and inflammation remains unknown [7,8,9,10,11]
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