title: High fat diet-induced non alcoholic fatty liver disease in rats is associated with hyperhomocysteinemia caused by down regulation of the transsulphuration pathway.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cellular Biology and Neuroscience, Istituto Superiore Sanità, Rome, Italy. elena.bravo@iss.it
authors.forename: Elena
authors.initials: E
authors.lastname: Bravo
authors.forename: Simonetta
authors.initials: S
authors.lastname: Palleschi
authors.forename: Patricia
authors.initials: P
authors.lastname: Aspichueta
authors.forename: Xabier
authors.initials: X
authors.lastname: Buqué
authors.forename: Barbara
authors.initials: B
authors.lastname: Rossi
authors.forename: Ainara
authors.initials: A
authors.lastname: Cano
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Napolitano
authors.forename: Begoña
authors.initials: B
authors.lastname: Ochoa
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Botham
mesh_terms: D000818:Animals; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D004041:Dietary Fats; D015536:Down-Regulation; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism; D006710:Homocysteine / Q000097:blood; D020138:Hyperhomocysteinemia / Q000209:etiology* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic; D014280:Triglycerides / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D007328:Insulin; D014280:Triglycerides; D006710:Homocysteine; D008780:Methyltransferases; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase