Abstract 433: Overexpression of Catalase Negates the Beneficial Effects of Dietary Lipids on Plasma Triglycerides and APOA1/C3/A5 Levels
Linoleic acid (LA) and oxidized linoleic acid (OxLA) are major components of Western diet. Both these lipids exert their actions through induction of oxidative stress. Our earlier studies have shown that feeding these dietary lipids to C57Bl/6 mice for two weeks decreased plasma triglyceride levels and up-regulated ApoA5 levels. We hypothesized that decreasing oxidative stress by overexpressing antioxidant Catalase in mice will block these beneficial effects. Methods: 24 male C57Bl/6 mice and 17 male Catalase (CAT) transgenic mice (8-12 weeks old) were divided into three groups each. Each group were fed orally either vehicle alone (ethanol), LA or OxLA (18mg/day) for 2 weeks. At the end of two weeks, the mice were sacrificed and plasma lipid profile along with liver mRNA and protein levels of Catalase and APOA1/C3/A5 was analyzed. Results: LA and OxLA feeding significantly decreased plasma triglycerides in C57Bl/6 mice but not other lipid cholesterols. However, no such changes were observed upon LA or OxLA feeding in CAT mice. The CAT mice expressed significantly higher mRNA levels of liver catalase but decreased APOA1/C3/A5 expression compared to C57Bl/6 mice, which was unaltered by LA or OxLA feeding. These effects were mediated by the modulation of the transcription factor, peroxisome proliferator-activated receptors (PPARs). Conclusion: In conclusion, overexpression of an antioxidant enzyme, catalase negated the beneficial effect of dietary lipids on triglyceride levels by altering the APOA1/C3/A5 pathway through modulation of PPARs. Our results suggest that a minimal level of oxidative stress is beneficial.
- © 2012 by American Heart Association, Inc.