A minimal model for hepatic fatty acid balance during fasting: Application to PPAR alpha-deficient mice

Pierre Blavy (1, 2) , Florence Gondret (2) , Hervé Guillou (3) , Sandrine Lagarrigue (4, 5) , P.G.P. Martin (3) , Jaap J. van Milgen (2) , Ovidiu Radulescu (6, 7, 1) , A. Siegel (8, 1, 9)

1 SYMBIOSE - Biological systems and models, bioinformatics and sequences
2 SENAH - Systèmes d'élevage, nutrition animale et humaine
3 Laboratoire de Pharmacologie et Toxicologie, UR66, INRA
4 GARen - Génétique Animale
5 GFAS - Génétique fonctionnelle, agronomie et santé [IFR 140]
6 UR - Université de Rennes
7 IRMAR - Institut de Recherche Mathématique de Rennes
8 CNRS - Centre National de la Recherche Scientifique
9 IRISA - Institut de Recherche en Informatique et Systèmes Aléatoires

The purpose of this study is to identify the hierarchy of importance amongst pathways involved in fatty acid (FA) metabolism and their regulators in the control of hepatic FA composition. A modeling approach was applied to experimental data obtained during fasting in PPAR_-knockout (KO) mice and wild-type mice. A step-by-step procedure was used in which a very simple model was completed by additional pathways until the model fitted correctly the measured quantities of FA in the liver. The resulting model included FA uptake by the liver, FA oxidation, elongation and elongation and desaturation of FA, which were found active in both genotypes during fasting.

Mots clés: Modeling; Fatty acid metabolism; Systems biology; Fasting; Knockout mice; rat-liver peroxisomes; gene-expression; adipose-tissue; null mice; metabolism; oxidation; mammals; obesity; chain; mouse

Domaines: Génétique animale

Pierre Blavy, Florence Gondret, Hervé Guillou, Sandrine Lagarrigue, P.G.P. Martin, et al.. A minimal model for hepatic fatty acid balance during fasting: Application to PPAR alpha-deficient mice. Journal of Theoretical Biology, 2009, 261 (2), pp.266. ⟨10.1016/j.jtbi.2009.07.025⟩. ⟨hal-00559147⟩