Abstract
Background:
Intrauterine growth restriction (IUGR) increases the risk of adult-onset hypercholesterolemia. High-fat diet (HFD) consumption potentiates IUGR-induced increased cholesterol. Cholesterol is converted to bile acids by Cyp7a1 in preparation for excretion. We hypothesized that IUGR rats fed a HFD will have increased cholesterol, decreased Cyp7a1 protein levels, and decreased bile acids compared to control rats fed a HFD.
Methods:
At day 21, IUGR and control pups were placed on one of three diets: a regular chow or one of two HFDs containing 1% or 2% cholesterol. Cholesterol levels and hepatic Cyp7a1 protein levels were quantified a postnatal week 28.
Results:
Both HFDs increased serum cholesterol levels in control rats, and HFD fed IUGR rats had further increased serum cholesterol up to 35-fold. Both HFDs increased hepatic cholesterol levels, and IUGR further increased hepatic cholesterol levels up to fivefold. IUGR decreased hepatic Cyp7a1 protein up to 75%, and hepatic bile acids up to 54%.
Conclusion:
IUGR increased cholesterol and bile acids and decreased Cyp7a1 protein in rats fed a HFD without changing food intake. These findings suggest that IUGR increases the vulnerability of HFD fed rats to hypercholesterolemia via decreased cholesterol conversion to bile acids.
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Acknowledgements
We thank Amnon Schlegel, M.D., Ph.D., at the University of Utah for supplying antibodies and scientific direction. This research was conducted at the University of Utah, Salt Lake City, UT.
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Zinkhan, E., Chin, J., Zalla, J. et al. Combination of intrauterine growth restriction and a high-fat diet impairs cholesterol elimination in rats. Pediatr Res 76, 432–440 (2014). https://doi.org/10.1038/pr.2014.117
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DOI: https://doi.org/10.1038/pr.2014.117
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