Natural abundance of nitrogen isotopes in amino acids are biomarkers of the metabolic syndrome onset

Jean-François Huneau (1) , Klaus-Jürgen Petzke (2) , Nathalie Poupin (3) , Tristan Mary-Huard (4) , Olivier Mantha (1) , Dominique Hermier (1) , François Mariotti (1) , Hélène Fouillet (1)

1 PNCA - Physiologie de la Nutrition et du Comportement Alimentaire
2 DIfE - German Institute of Human Nutrition Potsdam-Rehbrücke
3 ToxAlim-MeX - Métabolisme et Xénobiotiques
4 MIA-Paris - Mathématiques et Informatique Appliquées

Introduction: The isotope effects associated with nitrogen metabolic pathways result in differences in the nitrogen stable isotopecompositions (δ15N) of metabolic pools within individuals. Thus, inter-individual differences in some δ15N values can reflect differencesin nitrogen metabolismObjectives: Here, we evaluated in rats whether the metabolic syndrome (MS) onset involve some dysregulations of nitrogen metabolismwhich can be traced with δ15N values of individual amino acids in plasma and tissue proteins.Method / Design: Sixty male Wistar rats were fed a high fat diet for 10 weeks and 2 groups were selected in either the upper (MS group,n=10) or the lower (Lean, control group, L, n=10) ends of body weight and fasting insulin distributions and killed for tissue collection. Plasma and tissue proteins were precipitated and hydrolyzed and δ15N values of Ala, Asx, Glx, Gly, Leu, Pro and Ser were determined usinggas chromatograph combustion isotope ratio mass spectrometry.Results: Body weight and fasting insulin were 1.3 and 8.2 fold higher in the MS compared with the L group, respectively. No differencewas observed between groups for δ15N values of Asx, Glx, Leu, Pro and Ser, whereas δ15N values of Ala and Gly were significantly lowerin plasma and muscle proteins of the MS group. A discriminant analysis showed that the difference between δ15N of Gly and Leu in plasmaproteins is the main contributor to group separation. On the basis of this variable alone, 95% of the rats were correctly classified as MS or L.Conclusions: These results evidence that nitrogen metabolism is affected during the onset of insulin resistance in a tissue-specificmanner. They also suggest that the δ15N of some plasma amino acids represent promising early biomarkers of these metabolic changes.Keywords: (maximum 5): compound-specific amino acid δ15N values, early biomarkers, metabolic syndrome, protein and amino acidmetabolism

Mots clés: compound-specific amino acid delta 15N values; early biomarkers; protein and amino acid metabolism

Mots clés: metabolic syndrome

Domaines: Alimentation et Nutrition

Jean-François Huneau, Klaus-Jürgen Petzke, Nathalie Poupin, Tristan Mary-Huard, Olivier Mantha, et al.. Natural abundance of nitrogen isotopes in amino acids are biomarkers of the metabolic syndrome onset. 12th european nutrition conference, Oct 2015, Berlin, Germany. KARGER, 67, pp.1, 2015, Annals of Nutrition and Metabolism. ⟨hal-01572322⟩