TAILIEUCHUNG - Báo cáo khoa học: Fasting-induced oxidative stress in very long chain acyl-CoA dehydrogenase-deficient mice

Hepatopathy and hepatomegaly as consequences of prolonged fasting or illnesses are typical clinical features of very long chain acyl-CoA dehydro-genase (VLCACD) deficiency, the most common long-chain fatty acid b-oxidationdefect. Supplementationwithmedium-chain triglycerides (MCTs) is an important treatment measure in these defects, in order to supply suffi-cient energy. | ỊFEBS Journal Fasting-induced oxidative stress in very long chain acyl-CoA dehydrogenase-deficient mice Sara Tucci Sonja Primassin and Ute Spiekerkoetter Department of GeneralPediatrics University Children s Hospital Duesseldorf Germany Keywords fatty acid oxidation hepatopathy mediumchain triglyceride MCT oxidative stress very long chain acyl-CoA dehydrogenase VLCAD deficiency Correspondence S. Tucci Department of GeneralPediatrics University Children s Hospital MoorenstraBe 5 D-40225 Duesseldorf Germany Fax 49 211 811 6969 Tel 49 211 811 7685 E-mail Received 16 June 2010 revised 1 September 2010 accepted 9 September 2010 doi Hepatopathy and hepatomegaly as consequences of prolonged fasting or illnesses are typical clinical features of very long chain acyl-CoA dehydrogenase VLCACD deficiency the most common long-chain fatty acid b-oxidation defect. Supplementation with medium-chain triglycerides MCTs is an important treatment measure in these defects in order to supply sufficient energy. Little is known about the pathogenetic mechanisms leading to hepatopathy. Here we investigated the effects of prolonged fasting and an MCT diet on liver function. Wild-type WT and VLCAD knockout mice were fed with either a regular long-chain triglyceride diet or an MCT diet for 5 weeks. In both groups we determined liver and blood lipid contents under nonfasting conditions and after 24 h of fasting. Expression of genes regulating peroxisomal and microsomal oxidation pathways was analyzed by RT-PCR. In addition glutathione peroxidase and catalase activities as well as thiobarbituric acid reactive substances were examined. In VLCAD knockout mice fed with a long-chain triglyceride diet fasting is associated with excessive accumulation of liver lipids resulting in hepatopathy and strong upregulation of peroxisomal and microsomal oxidation pathways as well as antioxidant enzyme activities and thiobarbituric acid reactive .

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