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Modélisation comportementale du métabolisme interrégional de l'azote alimentaire et des cinétiques de l'urée à l'état nourri non stationnaire chez l'homme

Barbara Juillet 
Abstract : The assimilation of dietary proteins is a complex process associated with a cascade of transient and dynamic metabolic events, controlling the distribution of dietary amino acids in the splanchnic and peripheral areas. Compartmental modeling has already been demonstrated to enable analysis of clinical data obtained on this complex physiological system, and to allow a clearer understanding of its behaviour through an integrated approach. However, the pioneer work recently led in that area came up against a major difficulty: the difficulty to conduct the numerical identification of multicompartmental models, i.e., to estimate the numerical values for their parameters that will generate the predictions closest to the experimental data available on the system, especially when these data are scarce and scattered. In the continuity of this approach, the aim of our work was first to improve the techniques and rationalize the modeling methods available in our laboratory, and then to use our methodological developments to further study the metabolic phenomena involved in the postprandial specific valorisation of different protein sources under different nutritional conditions in humans. First, we were interested in the different steps of the development process of a complex multicompartmental model, which described the inter-organ distribution of dietary nitrogen during the postprandial phase in humans, from the collection of experimental data on the studied system to the structural and numerical identification of the model and its validation. In particular, we tried to simplify the critical step of the numerical identification of compartmental models and we developed a method which used an a priori sensitivity analysis of the system to divide the large and hardly solvable optimization problem into smaller subproblems, that were more easily solvable by classic search algorithms. These methodological developments allowed us to construct a new global model of dietary nitrogen metabolism in humans, describing the main processes involved in its postprandial utilization from its absorption to its regional assimilation and elimination out of the body. This model was developed using experimental data concerning the postprandial appearance of dietary nitrogen in certain accessible pools of the intestine, blood and urine in healthy subjects after ingestion of a solid mixed meal containing [15N]-labeled wheat protein. This model was then used and/or adapted to account for additional data obtained after ingestion of mixed meals containing milk or soy protein (liquid meals) or wheat protein (solid meal) under a similar experimental protocol, but conducted at two successive occasions in healthy subjects adapted to a normal, and then to a high, protein intake. The models thus developed enabled prediction of the gastrointestinal kinetics of dietary nitrogen under realistic, physiological conditions of ingesting mixed meals (bolus), and study of their impact on the subsequent metabolism of dietary nitrogen, in particular on its splanchnic anabolic and catabolic utilization. These models also allowed study of the influence of qualitative (nature of the protein source) and quantitative (habitual level of protein intake) factors of protein intake on the postprandial specific valorisation of dietary proteins. In particular, our work demonstrated the importance of the phenomenon of dietary nitrogen entero-hepatic recycling after ingestion of dietary proteins with a low nutritional value, such as wheat protein. Because of these results, we became more particularly interested in the postprandial urea kinetics, as well as their modulation by different dietary factors. For this purpose, we developed a regional model, which specifically described the splanchnic metabolic phenomena of deamination and entero-hepatic recycling. This model was actually a subsystem of the global models previously developed, and using data obtained only in blood and urine, it made it possible to study of the influence of qualitative and quantitative factors of protein intake on the postprandial kinetics of dietary and endogenous urea N production, excretion and hydrolysis. Our modeling work thus provided new and original information concerning the influence of different dietary factors on the postprandial metabolic fate of dietary nitrogen in humans. This work could be repeated and pursued by the analysis of other experimental data obtained under different physiopathological conditions in order to determine the nutritional strategies best adapted to these situations.
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Submitted on : Wednesday, July 4, 2007 - 8:00:00 AM
Last modification on : Wednesday, July 4, 2007 - 8:00:00 AM
Long-term archiving on: : Wednesday, September 8, 2010 - 5:31:06 PM


  • HAL Id : pastel-00002662, version 1



Barbara Juillet. Modélisation comportementale du métabolisme interrégional de l'azote alimentaire et des cinétiques de l'urée à l'état nourri non stationnaire chez l'homme. Life Sciences [q-bio]. INAPG (AgroParisTech), 2006. English. ⟨NNT : 2006INAP0031⟩. ⟨pastel-00002662⟩



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