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.
journal_name
Pediatr Resjournal_title
Pediatric researchauthors
Zinkhan EK,Chin JR,Zalla JM,Yu B,Numpang B,Yu X,Jiang C,Callaway CW,McKnight RA,Joss-Moore L,Lane RHdoi
10.1038/pr.2014.117subject
Has Abstractpub_date
2014-11-01 00:00:00pages
432-40issue
5eissn
0031-3998issn
1530-0447pii
pr2014117journal_volume
76pub_type
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