Overexpression of Catalase negates the beneficial effects of dietary lipids on plasma triglyceride and APOA1/C3/A5 pathway

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 showed 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 these mice will block this beneficial effects. Methods 24 male C57Bl/6 mice and 17 male Catalase (CAT) transgenic mice (18–28 g) at 8–12 weeks old were divided into three groups each. Each group was 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 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 compared to C57Bl/6 mice, which was unaltered by LA or OxLA feeding. 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. Support: NIH HL‐74239 &5P20RR016477