Influence des déterminants nutritionnels de l'homocystéine sur la stéatose hépatique chez le rongeur

Abstract : Homocysteine (Hcy) is a sulphur-containing amino acid that plays a central role in cellular methylation processes. hyperhomocysteinernia (HHcy) has been linked to various abnormalities occurring in liver, heart and brain. The relevant pathologies can range from hepatic steatosis to cardiovascular disease, neural tube defect and Alzheimer disease. Although the mechanisms for these are not clear, the perturbation of the SAM dependant transméthylation and the elevation of the oxidant stress could be involved in the pathogenesis of these diseases. The aim of this work was to deterrnine the factors leading from moderate or severe HHcy, to hepatic steatosis, a condition characterized by triglycerides accumulation that can lead to fibrosis and cirrhosis. ln addition, we have studied the changes of hepatic redox status as a consequence of HHcy. ln our study, we used 21 days-old young rats born to mothers that had undergone a feeding of methyl-donor deficient diet (in folate, vitamin B12 and choline) prior to the pregnancy. The maternal deficiency in methyl donor, induced in these pups moderate HHcy. Additionally, hepatic steatosis appeared in these pups. HHcy induced the drop of the SAM/SAH ratio and 100 to a decrease in camitine synthesis, causing the hepatic steatosis. We found that Hcy accumulation also 100 to an increase of the oxidant stress. ln transgenic mice cbs -/-, there is SAH accumulation, potent inhibitor of methyltransferases, that disturbs Hcy remethylation cycle. So, we have established a relationship between Hcy remethylation, camitine synthesis and hepatic steatosis using the moderate HHcy nutritional model through using the methyl deficient diet.
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Jean-Marc Alberto. Influence des déterminants nutritionnels de l'homocystéine sur la stéatose hépatique chez le rongeur. Sciences agricoles. Université Henri Poincaré - Nancy 1, 2006. Français. ⟨NNT : 2006NAN11316⟩. ⟨tel-01754345⟩

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