Abstract
On an organismal level, metabolism needs to react in a well-orchestrated manner to metabolic challenges such as nutrient uptake. Key metabolic hubs in human blood are pyruvate and lactate, both of which are constantly interconverted by very fast exchange fluxes. The quantitative contribution of different food sources to these metabolite pools remains unclear. Here, we applied in vivo stable isotope labeling to determine postprandial metabolic fluxes in response to two carbohydrate sources of different complexity. Depending on the ingested carbohydrate source, glucose or wheat flour, the net direction of the lactate dehydrogenase, and the alanine amino transferase fluxes were adjusted in a way to ensure sufficient availability, while, at the same time, preventing an overflow in the respective metabolite pools. The systemic lactate pool acts as a metabolic buffer which is fueled in the early- and depleted in the late-postprandial phase and thus plays a key role for systemic metabolic homeostasis.
Highlights
When a healthy individual in fasting state is challenged with a nutritional intervention such as a meal, the metabolism is confronted with an excessive supply of nutrients causing metabolite levels in the blood to increase and homeostasis to be out of balance
We separated the entire postprandial phase into two windows, the absorptive (0–90min) and the post-absorptive phase (90–360 min), as underlying metabolic fluxes are adapted in a time and intervention dependent manner (Figure 8)
Two factors predominantly contributed to this phenotype, namely (I) the trend observed toward a delay in glucose appearance and (II) the availability of protein-derived alanine being converted into pyruvate
Summary
When a healthy individual in fasting state is challenged with a nutritional intervention such as a meal, the metabolism is confronted with an excessive supply of nutrients causing metabolite levels in the blood to increase and homeostasis to be out of balance. Systemic metabolism has to rapidly undergo complex adaptions to switch from the former catabolic to the anabolic state to keep the systemic concentrations of food-derived nutrients including glucose, amino acids and fatty acids in a physiological range [1–3]. The goal to understand or even predict postprandial metabolism, has been approached by nutritional research in several ways. Complex isotopic labeling experiments employing dual or even triple tracer based approaches determine highly accurate metabolic flux information and provide a better mechanistic understanding, but are usually limited to the kinetics of single metabolites, in most cases glucose [9–11]. To gain quantitative flux information of an entire metabolic network in the postprandial phase, a setting
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