La programmation fœtale de la carence en donneurs de méthyles entraîne une stéato-hépatite chez les rats soumis à un régime hyper-énergétique au cours de la vie adulte

Abstract : The influence of fetal programming hypothesis on non-alcoholic steato-hepatitis (NASH) has deserved insufficient interest. Methyl donor deficiency during pregnancy and lactation is frequent in population and is an experimental model of fetal programming. In this model, it produces a liver steatosis in 21 days old pups, which results from decreased fatty acid oxidation. We evaluated the effects of fetal programming on NASH in Wistar rats born from mothers fed either a control or a methyl donor deficient (iMDD) diet during pregnancy and lactation. Pups received a control diet after weaning (D21 to D50) and a part from adult rats were fed with an high-fat diet (HF) (D50 to D185). Animals were sacrificed at D50 and D185. In D50 iMDD rats, we observed an increased abdominal fat and ASAT/ALAT ratio, but no liver histological abnormality. However, D185 iMDD/HF rats have developed NASH, with hallmarks of insulin resistance and increased expression of several genes and proteins involved in inflammasome, stellate cell stimulation, fibrosis and tissu remodelling, including AngII, TGFβ1 and NFκB. In conclusion, MDD during pregnancy and lactation produces NASH in animals subjected subsequently to an high-fat diet during adulthood, despite the recovery of a control diet. These results suggest that MDD during pregnancy is a risk factor of NASH development in subjects subsequently exposed to high-fat diet.
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Anaïs Bison. La programmation fœtale de la carence en donneurs de méthyles entraîne une stéato-hépatite chez les rats soumis à un régime hyper-énergétique au cours de la vie adulte. Biologie animale. Université de Lorraine, 2015. Français. ⟨NNT : 2015LORR0285⟩. ⟨tel-02321736⟩

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