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Postprandial metabolic events in mini-pigs: new insights from a combined approach using plasma metabolomics, tissue gene expression, and enzyme activity

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Abstract

To unravel metabolic adaptations preceding the occurrence of metabolic dysregulations, a nutritional challenge appears as the best tool capable to reveal metabolic disturbances compared to single-point measurements at the static fasting (PA) state. The aim of the present work was to study the metabolic trajectories at the postprandial (PP) state in a relevant human nutrition animal model combining plasma metabolome analysis with classical metabolism exploration tools. In a first trial, three mini pigs were fed a test meal and arterial blood samples withdrawn before and over 4 h following the meal for plasma metabolites analysis (LC–MS and classical biochemistry). In a second trial, three mini-pigs were euthanized after an overnight fasting and three others 1:15 h after the test meal. The metabolism was explored at the molecular (mRNA levels), biochemical (enzyme activities) and signalling (phosphorylation status) levels in the liver and muscle. As expected, and in accordance with alterations in plasma glucose, urea levels, gluconeogenesis/glycolysis/lipid and amino acid (AA) oxidation genes expression and enzymes activities, the metabolomic approach discriminated the PA from the PP state (R2Ycum = 0.991; Q2Ycum = 0.921). More interestingly hierarchical cluster analysis revealed that the PP metabolome included actually four types of kinetic profiles. Further, PLS-DA analysis revealed a two-step pattern: 1–2  and 3–4 h (R2Ycum = 0.837; Q2cum = 0.635). Among the molecules explaining this discrimination, several AAs and phospholipid species were highlighted and their significance in PP metabolism discussed. Our data showed that the combination of these approaches in mini-pigs could be used to investigate PP metabolic adaptations in various physiological and patho-physiological states.

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Acknowledgments

The authors acknowledge D. Durand, C. Prolhac, C. Buisson, J. David, M. Petera and the personnel of the Animal Facility (C. de L’Homme, B. Cohade) for technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

Compliance with Ethical Requirements

All procedures were in accordance with the guidelines formulated by the European Community for the use of experimental animals (L358-86/609/EEC, Council Directive, 1986).

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Authors and Affiliations

  1. Unité de Nutrition Humaine, Clermont Université, Université d’Auvergne, BP 10448, 63000, Clermont-Ferrand, France

    Sergio Polakof, Didier Rémond, Mathieu Rambeau, Estelle Pujos-Guillot, Jean-Louis Sébédio, Dominique Dardevet, Blandine Comte & Isabelle Savary-Auzeloux

  2. INRA, UMR 1019, UNH, CRNH Auvergne, 63000, Clermont-Ferrand, France

    Sergio Polakof, Didier Rémond, Mathieu Rambeau, Estelle Pujos-Guillot, Jean-Louis Sébédio, Dominique Dardevet, Blandine Comte & Isabelle Savary-Auzeloux

  3. INRA, UMR 1019, Plateforme d’Exploration du Métabolisme, UNH, 63000, Clermont-Ferrand, France

    Estelle Pujos-Guillot

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  1. Sergio Polakof
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Correspondence to Sergio Polakof.

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Polakof, S., Rémond, D., Rambeau, M. et al. Postprandial metabolic events in mini-pigs: new insights from a combined approach using plasma metabolomics, tissue gene expression, and enzyme activity. Metabolomics 11, 964–979 (2015). https://doi.org/10.1007/s11306-014-0753-8

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