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La stéatose hépatique chez le canard mulard : étude cinétique du métabolisme intermédiaire, stress cellulaire, autophagie et nouvelle approche par les microARNs

Tracy Pioche
Abstract : The main objective of this thesis was to continue the investigations carried out on the mechanisms underlying the development of foie gras in mule ducks. This process, known as hepatic steatosis and induced by overfeeding, needs to be further studied in order to contribute to overfeeding optimization.A kinetic study of the expression of genes related to hepatic steatosis, intermediate metabolism and cellular stress in mule ducks highlighted firstly the strong mobilization of carbohydrate and lipid metabolisms. Secondly a significant induction of the insulin / mTOR signalling pathway and the activation of various cellular protection mechanisms in hepatocytes were observed allowing them to fight against the increased intake of starch brought by the overfeeding. Among these are various protective mechanisms, autophagy has been the subject of extensive study in overfed ducks whose steatosis has been barely induced compared to non-overfed ducks. Autophagic flux measurements (LC3-II) showed that overfeeding induced inhibition of the autophagic process in mule ducks’ hepatocytes from the early stage of hepatic steatosis. This same study found that the mechanisms associated with cellular stress such as oxidative stress, endoplasmic reticulum stress or apoptosis did not occur early in the development of hepatic steatosis but much later. The same is true for the impact of overfeeding on mTOR signalling pathway.In addition, the kinetic study also revealed the significant induction of cholesterol metabolism correlated with the liver weight gain of ducks during overfeeding. These results aroused the interest of investigating plasma biomarkers for the development of hepatic steatosis related to cholesterol metabolism among microRNAs. Thus, duck's plasmatic miRNome was sequenced and it allowed to define the most differentially expressed microRNAs in the plasma of mule ducks but also to detect microRNAs (miR-122, miR-107 and mi-R194) as potential biomarkers that could be used for monitoring the development of fatty liver.All of this work contributes to the advancement of research on understanding the mechanisms of establishment of hepatic steatosis in mule ducks.
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Tracy Pioche. La stéatose hépatique chez le canard mulard : étude cinétique du métabolisme intermédiaire, stress cellulaire, autophagie et nouvelle approche par les microARNs. Sciences agricoles. Université de Pau et des Pays de l'Adour, 2019. Français. ⟨NNT : 2019PAUU3043⟩. ⟨tel-02881956⟩

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