Une nouvelle approche d’isotopomique pour identifier les dysrégulations du métabolisme des protéines et des acides aminés lors du développement du syndrome métabolique

Abstract : Although the different components of the metabolic syndrome (MS) are likely to affect protein and amino acid (AA) metabolism, the available data are few and often contradictory, due to the heterogeneity of presentation of this syndrome and the limitations of classical approaches to investigate nitrogen metabolism. The present thesis work uses a novel isotopomic approach, based on the measurement of the natural abundance of stable isotopes of nitrogen (δ15N) and carbon (δ13C) in tissue proteins and AA to identify alterations in protein metabolism occurring during the nutritional induction of MS in rats. Our results allow to validate experimentally the predictions of a multi-compartimental model developed in the laboratory and showing that the δ15N reflects the differential orientation of AA between anabolic (proteosynthesis) and catabolic (oxidation) pathways. We have also shown that under certain conditions, the δ13C can allow to estimate the proportion of carbons in AA and tissue proteins issuing from dietary proteins, carbohydrates and lipids respectively, thus providing information on the metabolic flexibility of individuals. The measurements of δ15N and δ13C in proteins and AA, alone or combined with the measurement of protein synthesis rates after administration of deuterated water, then allowed us to highlight the changes in protein and AA metabolism occurring during perinatal and post-weaning exposure to a high-fat high-sugar diet, as well as those associated with individual differences in sensitivity to the induction of a MS by the same kind of diet. These alterations are tissuespecific and differ according to whether they result solely from differences in individual sensitivity to diet or whether they are also attributable to differences in the carbohydrate/lipid balance of the diet. Altogether, our results show that the development of MS is associated with changes in AA metabolic partitioning between the anabolic and oxidative pathways, differently affecting the liver, muscle, intestine and adipose tissue, and with an altered metabolic flexibility in muscle. This work opens the way to human studies, based on the measurements of δ15N and δ 13C in accessible pools.
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Olivier Landry Mantha. Une nouvelle approche d’isotopomique pour identifier les dysrégulations du métabolisme des protéines et des acides aminés lors du développement du syndrome métabolique. Alimentation et Nutrition. Université Paris-Saclay, 2018. Français. ⟨NNT : 2018SACLA009⟩. ⟨tel-02182659⟩

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