Abstract | BACKGROUND AND AIM: METHODS: RESULTS: As expected, FO feeding led to robust hepatic PPARalpha 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-kappaB activation or enhanced cyclooxygenase-2 activity. CONCLUSIONS: Feeding an n-3 PUFA-enriched diet activated PPARalpha 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 PPARalpha activation, and could also be responsible for lipotoxic hepatocellular injury and inflammatory recruitment.
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Authors | Claire Z Larter, Matthew M Yeh, Jenny Cheng, Jacqueline Williams, Sandie Brown, Aileen dela Pena, Kim S Bell-Anderson, Geoffrey C Farrell |
Journal | Journal of gastroenterology and hepatology
(J Gastroenterol Hepatol)
Vol. 23
Issue 2
Pg. 267-75
(Feb 2008)
ISSN: 1440-1746 [Electronic] Australia |
PMID | 17868330
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Dietary Fats, Unsaturated
- Fatty Acids
- Fatty Acids, Omega-3
- Fish Oils
- Lipid Peroxides
- PPAR alpha
- Methionine
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Topics |
- Animals
- Choline Deficiency
(complications)
- Dietary Fats, Unsaturated
(pharmacology)
- Disease Models, Animal
- Down-Regulation
- Fatty Acids
(biosynthesis)
- Fatty Acids, Omega-3
(pharmacology)
- Fatty Liver
(etiology, physiopathology, prevention & control)
- Female
- Fish Oils
(pharmacology)
- Gene Expression
(drug effects)
- Lipid Peroxides
(metabolism)
- Lipogenesis
(drug effects)
- Lipolysis
(genetics)
- Liver
(metabolism)
- Methionine
(deficiency)
- Mice
- Mice, Inbred C57BL
- PPAR alpha
(metabolism)
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