Impact of GPX1 null and GPX4 hemizygosity on plasma lipid profiles of mice fed a high fat diet

Several studies have shown possible involvements of selenium‐dependent GPX1 and GPX4 in lipid metabolism. Two experiments were conducted to assess impacts of GPX1 null (gpx1 −/− ) and GPX4 hemizygosity (gpx4 +/− ) on plasma triglycerides, cholesterol, and free fatty acid concentrations in female mice fed a high fat diet (58% calories from fat) containing 28% coconut butter. Prior to both experiments, mice were fed a torula‐yeast‐sucrose based diet. In Experiment 1, six gpx1 −/− and four wild type (WT) mice (3 months of age) were fed the high fat diet for two months. Initial plasma triglyceride and free fatty acid concentrations of gpx1 −/− mice were 15% (P = 0.08) and 25% (P = 0.07) greater than those of WT mice, respectively. After feeding high fat diet for two months, plasma concentration of cholesterol and triglyceride in gpx1 −/− mice were 15% (P = 0.1) higher and 28% (P = 0.1) lower than those of WT mice, respectively. In Experiment 2, five gpx4 +/− and four WT mice (2 months of age) were fed the high fat diet for four months. Initial plasma triglyceride concentration in gpx4 +/− mice was 23% (P = 0.8) lower than that of WT mice. After feeding the high fat diet for four months, both genotypes showed similar increase (+125%) in plasma triglyceride concentrations. Plasma cholesterol concentration of gpx4 +/− mice was 14% (P = 0.09) lower than that of WT mice. In conclusion, GPX1 null and GPX4 haploid insufficiency exerted moderate impacts on plasma lipid profiles in young adult female mice fed a high fat diet. (NIH DK 53018 TO XGL)