High fat diet-induced non alcoholic fatty liver disease in rats is associated with hyperhomocysteinemia caused by down regulation of the transsulphuration pathway

Lipids in Health and Disease

Research

Elena Bravo¹  Mariarosaria Napolitano¹  Simonetta Palleschi²  Barbara Rossi²  Ainara Cano³  Begoña Ochoa³  Patricia Aspichueta³  Xabier Buqué³  Kathleen M Botham⁴ 

[1] Department of Cellular Biology and Neuroscience, Istituto Superiore Sanità, Rome, Italy;Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome, Italy;Department of Physiology, University of the Basque Country Faculty of Medicine and Dentistry, Leioa, Spain, Sarriena s/n, 48940, Rome, Italy;Department of Veterinary Basic Sciences, the Royal Veterinary College, Royal College St., NW1 0TU, London, UK;

关键词: Homocysteine;    hyperhomocysteinemia;    non alcoholic fatty liver disease;    transsulphuration pathway;   

DOI  :  10.1186/1476-511X-10-60

 received in 2011-03-03, accepted in 2011-04-19,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundHyperhomocysteinemia (HHcy) causes increased oxidative stress and is an independent risk factor for cardiovascular disease. Oxidative stress is now believed to be a major contributory factor in the development of non alcoholic fatty liver disease, the most common liver disorder worldwide. In this study, the changes which occur in homocysteine (Hcy) metabolism in high fat-diet induced non alcoholic fatty liver disease (NAFLD) in rats were investigated.Methods and resultsAfter feeding rats a standard low fat diet (control) or a high fat diet (57% metabolisable energy as fat) for 18 weeks, the concentration of homocysteine in the plasma was significantly raised while that of cysteine was lowered in the high fat as compared to the control diet fed animals. The hepatic activities of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGS), the enzymes responsible for the breakdown of homocysteine to cysteine via the transsulphuration pathway in the liver, were also significantly reduced in the high fat-fed group.ConclusionsThese results indicate that high fat diet-induced NAFLD in rats is associated with increased plasma Hcy levels caused by down-regulation of hepatic CBS and CGL activity. Thus, HHcy occurs at an early stage in high fat diet-induced NAFLD and is likely to contribute to the increased risk of cardiovascular disease associated with the condition.

【 授权许可】

CC BY   
© Bravo et al; licensee BioMed Central Ltd. 2011