15. Behavioural analysis of the fasting substrate conversion for energy utilization in growing pigs using within-day kinetics in the DyNAMPig model
Résumé
Homeostasis of metabolite pools in pigs is challenged when confronted with a rapid post-absorptive influx of nutrients. Physiological mechanisms that buffer this influx are key in overcoming this challenge, e.g. by storing excess absorbed glucose as glycogen. On the other hand, utilization of these body stores for energy in between meals ensures energy is available during fasting by providing oxidizable substrates (glucose, fatty acids). With our current development of an in-silico nutrient-based post-absorptive metabolism model using withinday kinetics (DyNAMPig), a representation of these mechanisms is included to accommodate predictions of the post-absorptive metabolic fate of nutrients in growing pigs. Here, we present a showcase of the conversion of body stores to metabolite pools in between meals.
Principles for nutrient partitioning were adapted from the pig growth model developed by Halas et al. (2004) and modified to accommodate within-day kinetics of nutrient metabolism. Body components (protein, fat) and metabolites (glucose, glycogen, fatty acids, acetyl-CoA and amino acids) are represented as eleven whole-body pools connected by fluxes their respective deposition, breakdown, storage and partitioning. Fluxes use Michaelis-Menten kinetics to represent the inhibition and affinity aspects of nutrient partitioning. Parameters describing the rate and type of within-day nutrient utilization are currently calibrated to indirect calorimetry data.
Substrate conversion rates for (A) body fat mobilization, (B) glycogenolysis and (C) amino acid degradation for either energy or gluconeogenesis, over a two-day period of a pig fed a restricted diet (30% and 70% of total daily feed intake in a morning and afternoon meal respectively) are shown in Fig. 1. Presented values are to be fine-tuned in the current calibration. In general, all three substrate utilizations are responding according to expectations, being low following the influx of nutrients during and immediately after meals and increasing in periods of fasting. The majority of energy during fasting periods is provided by lipolysis, consistent with in vivo observations. Glycogen utilization precedes lipolysis, which increases in time as glycogen stores start to become depleted. Amino acid degradation is negatively correlated with glycogenolysis, implying that glucose homeostasis is achieved by increasingly utilizing amino acids as a source of glucose when there is insufficient influx of glucose via either a meal or glycogenolysis.
In conclusion, providing sources of energy during fasting for pigs using storage pools is a promising new direction for the modelling of nutrient utilization in pigs using within-day kinetics. It allows modelling the effects of variation in nutrient absorption kinetics, and provides a basis for the incorporation of more biological processes in whole-animal models. Further calibration of these mechanisms to within-day energy utilization data is required to ensure overall partitioning of nutrients adheres to in vivo data.