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

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

Author Affiliations

1 Department of Cellular Biology and Neuroscience, Istituto Superiore Sanità, Rome, Italy

2 Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome, Italy

3 Department of Physiology, University of the Basque Country Faculty of Medicine and Dentistry, Sarriena s/n, 48940 Leioa, Spain. Rome, Italy

4 Department of Veterinary Basic Sciences, the Royal Veterinary College, Royal College St., London NW1 0TU, UK

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Lipids in Health and Disease 2011, 10:60  doi:10.1186/1476-511X-10-60

Published: 19 April 2011



Hyperhomocysteinemia (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 results

After 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.


These 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.

Homocysteine; hyperhomocysteinemia; non alcoholic fatty liver disease; transsulphuration pathway