PMID- 21504583 OWN - NLM STAT- MEDLINE DCOM- 20110907 LR - 20211020 IS - 1476-511X (Electronic) IS - 1476-511X (Linking) VI - 10 DP - 2011 Apr 19 TI - High fat diet-induced non alcoholic fatty liver disease in rats is associated with hyperhomocysteinemia caused by down regulation of the transsulphuration pathway. PG - 60 LID - 10.1186/1476-511X-10-60 [doi] AB - 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. 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 beta-synthase (CBS) and cystathionine gamma-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. FAU - Bravo, Elena AU - Bravo E AD - Department of Cellular Biology and Neuroscience, Istituto Superiore Sanita, Rome, Italy. elena.bravo@iss.it FAU - Palleschi, Simonetta AU - Palleschi S FAU - Aspichueta, Patricia AU - Aspichueta P FAU - Buque, Xabier AU - Buque X FAU - Rossi, Barbara AU - Rossi B FAU - Cano, Ainara AU - Cano A FAU - Napolitano, Mariarosaria AU - Napolitano M FAU - Ochoa, Begona AU - Ochoa B FAU - Botham, Kathleen M AU - Botham KM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110419 PL - England TA - Lipids Health Dis JT - Lipids in health and disease JID - 101147696 RN - 0 (Dietary Fats) RN - 0 (Insulin) RN - 0 (Triglycerides) RN - 0LVT1QZ0BA (Homocysteine) RN - EC 2.1.1.- (Methyltransferases) RN - EC 4.2.1.22 (Cystathionine beta-Synthase) RN - EC 4.4.1.1 (Cystathionine gamma-Lyase) SB - IM MH - Animals MH - Cystathionine beta-Synthase/metabolism MH - Cystathionine gamma-Lyase/metabolism MH - *Dietary Fats MH - Down-Regulation MH - Fatty Liver/*etiology/metabolism MH - Homocysteine/blood MH - Hyperhomocysteinemia/*etiology/metabolism MH - Insulin/blood MH - Liver/metabolism MH - Male MH - *Metabolic Networks and Pathways MH - Methyltransferases/genetics/metabolism MH - Non-alcoholic Fatty Liver Disease MH - Rats MH - Rats, Wistar MH - Transcription, Genetic MH - Triglycerides/metabolism PMC - PMC3096990 EDAT- 2011/04/21 06:00 MHDA- 2011/09/08 06:00 PMCR- 2011/04/19 CRDT- 2011/04/21 06:00 PHST- 2011/03/03 00:00 [received] PHST- 2011/04/19 00:00 [accepted] PHST- 2011/04/21 06:00 [entrez] PHST- 2011/04/21 06:00 [pubmed] PHST- 2011/09/08 06:00 [medline] PHST- 2011/04/19 00:00 [pmc-release] AID - 1476-511X-10-60 [pii] AID - 10.1186/1476-511X-10-60 [doi] PST - epublish SO - Lipids Health Dis. 2011 Apr 19;10:60. doi: 10.1186/1476-511X-10-60.