title: Combination of intrauterine growth restriction and a high-fat diet impairs cholesterol elimination in rats.
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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Erin K
authors.initials: EK
authors.lastname: Zinkhan
authors.affiliation: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah.
authors.forename: Jeanette R
authors.initials: JR
authors.lastname: Chin
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Zalla
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Baifeng
authors.initials: B
authors.lastname: Yu
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Ben
authors.initials: B
authors.lastname: Numpang
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Xing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Chengshe
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Callaway
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Robert A
authors.initials: RA
authors.lastname: McKnight
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Lisa
authors.initials: L
authors.lastname: Joss-Moore
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lane
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004435:Eating; D005227:Fatty Acids / Q000097:blood; D005260:Female; D005317:Fetal Growth Retardation; D006937:Hypercholesterolemia / Q000097:blood / Q000201:enzymology / Q000209:etiology*; D008099:Liver / Q000201:enzymology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation; D015430:Weight Gain
chemical_list: D001647:Bile Acids and Salts; D015415:Biomarkers; D005227:Fatty Acids; D002784:Cholesterol; C532838:CYP7A1 protein, rat; D002790:Cholesterol 7-alpha-Hydroxylase