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43: Fetal programming of hypercholesterolemia and hypertriglyceridemia is evident in young adulthood

      Objective

      We have previously described a model of developmental programming of atherosclerosis in which heterozygous mice born to apoE-knockout mothers were affected by high cholesterol levels, atherosclerotic plaques, and renal and hepatic lesions at 8 months of age. Our objective in this study was to determine whether this process can be detected earlier in life.

      Study Design

      We crossbred apoE knockout (apoE−/−) and wild-type C57BL/6J (apoE+/+) mice to obtain heterozygous offspring born to hypercholesterolemic apoE−/− mothers (apoE+/−mat, n=17), heterozygous offspring born to wild-type mothers (apoE+/−pat, n=16), homozygous knockout offspring (apoE−/−, n=18), and homozygous wild-type offspring (apoE+/+, n=17). The resulting pups were followed until 4 months of age when they were sacrificed. Serum samples were obtained, and levels of total cholesterol and total triglycerides were measured using colorimetric enzyme assays.

      Results

      At 4 months of age, we found significant differences in total cholesterol and triglyceride levels across the study groups (p<0.001 and p<0.007, respectively). Total cholesterol levels in apoE+/−mat offspring were higher than in apoE+/−pat (p<0.001) and apoE+/+ (p=0.006), and lower than in apoE−/− (p<0.001) offspring. Triglyceride levels were similar in apoE+/−mat and apoE−/− animals. ApoE+/−mat displayed higher triglyceride concentrations than apoE+/+ mice (p=0.006), while the difference with apoE+/−pat offspring did not reach statistical significance (p=0.137).
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      Conclusion

      The present data validate our previous finding of a significant effect of the maternal environment on cholesterol levels in the apoE mouse model. In addition, we have found that the effect on cholesterol and triglyceride levels is demonstrable in the offspring during young adulthood, providing an early opportunity for prevention of adult diseases.