Combination of intrauterine growth restriction and a high-fat diet impairs cholesterol elimination in rats. Pediatr Res 2014 Nov;76(5):432-40
Date
08/15/2014Pubmed ID
25119340DOI
10.1038/pr.2014.117Scopus ID
2-s2.0-84908600019 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
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.
Author List
Zinkhan EK, Chin JR, Zalla JM, Yu B, Numpang B, Yu X, Jiang C, Callaway CW, McKnight RA, Joss-Moore L, Lane RHMESH terms used to index this publication - Major topics in bold
AnimalsBile Acids and Salts
Biomarkers
Cholesterol
Cholesterol 7-alpha-Hydroxylase
Diet, High-Fat
Disease Models, Animal
Eating
Fatty Acids
Female
Fetal Growth Retardation
Hypercholesterolemia
Liver
Male
Pregnancy
Prenatal Exposure Delayed Effects
Rats, Sprague-Dawley
Time Factors
Up-Regulation
Weight Gain
