We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Activation of peroxisome proliferator-activated receptor α by dietary fish oil attenuates steatosis, but does not prevent experimental steatohepatitis because of hepatic lipoperoxide accumulation.
- Authors
Larter, Claire Z.; Yeh, Matthew M.; Cheng, Jenny; Williams, Jacqueline; Brown, Sandie; dela Pena, Aileen; Bell-Anderson, Kim S.; Farrell, Geoffrey C.
- Abstract
Background and Aim: Non-alcoholic fatty liver disease is the result of an imbalance in hepatic lipid partitioning that favors fatty acid synthesis and storage over fatty acid oxidation and triglyceride secretion. The progressive, inflammatory disorder of steatohepatitis can be prevented or reversed by correcting this lipid imbalance by activating peroxisome proliferator-activated receptor (PPAR) α, a transcription factor which regulates fatty acid oxidation. n-3 polyunsaturated fatty acids (PUFA), such as those found in fish oil (FO), are naturally occurring PPARα ligands which also suppress lipid synthesis. Methods: We tested the role of dietary activation of PPARα by feeding mice a n-3 PUFA-enriched FO diet in the methionine and choline deficient (MCD) model of steatohepatitis. Results were compared with mice fed the corresponding diet supplemented with monounsaturated fatty acids as olive oil (OO). Results: As expected, FO feeding led to robust hepatic PPARα activation in control mice, and decreased expression of genes involved with fatty acid synthesis. Such lipolytic gene expression profile was also clearly evident in FO MCD-fed mice, and was associated with reduced hepatic lipid accumulation in comparison with mice fed OO MCD diet. FO feeding in control mice also caused marked hepatic accumulation of lipoperoxides compared with OO and chow-fed mice. This was further exacerbated in FO MCD-fed animals, which developed steatohepatitis characterized by mild steatosis and moderate inflammation in comparison with OO MCD-fed mice; such inflammatory recruitment was not related to NF-κB activation or enhanced cyclooxygenase-2 activity. Conclusions: Feeding an n-3 PUFA-enriched diet activated PPARα and suppressed hepatic de novo lipogenesis, but failed to prevent development of steatohepatitis in the presence of methionine and choline deficiency. Instead, the very high levels of hepatic lipoperoxides may have abrogated the protection that would otherwise be conferred by PPARα activation, and could also be responsible for lipotoxic hepatocellular injury and inflammatory recruitment.
- Subjects
LIVER diseases; FATTY degeneration; PEROXISOMES; TRIGLYCERIDES; TRANSCRIPTION factors; LIPID synthesis; PEROXIDATION
- Publication
Journal of Gastroenterology & Hepatology, 2008, Vol 23, Issue 2, p267
- ISSN
0815-9319
- Publication type
Article
- DOI
10.1111/j.1440-1746.2007.05157.x