title: Intrauterine growth restriction combined with a maternal high-fat diet increases hepatic cholesterol and low-density lipoprotein receptor activity in rats.
abstract: Intrauterine growth restriction (IUGR) and maternal consumption of a high-saturated-fat diet (HFD) increase the risk of hypercholesterolemia, a leading cause of morbidity and mortality. Many pregnant women eat a HFD, thus exposing the fetus to a HFD in utero. The cumulative effect of in utero exposure to IUGR and a HFD on offspring cholesterol levels remains unknown. Furthermore, little is known about the mechanism through which IUGR and maternal HFD consumption increase cholesterol. We hypothesize that IUGR combined with a maternal HFD would increase offspring serum and hepatic cholesterol accumulation via alteration in levels of key proteins involved in cholesterol metabolism. To test our hypothesis we used a rat model of surgically induced IUGR and fed the dams a regular diet or a HFD HFD-fed dams consumed the same kilocalories as regular diet-fed dams, with no difference between surgical intervention groups. In the offspring, IUGR combined with a maternal HFD increased hepatic cholesterol levels, low-density lipoprotein (LDL) receptor protein levels, and Ldlr activity in female rat offspring at birth and both sexes at postnatal day 14 relative to non-IUGR offspring both from regular diet- and HFD-fed dams. These findings suggest that IUGR combined with a maternal HFD increases hepatic cholesterol accumulation via increased LDL cholesterol uptake into the liver with resulting persistent increases in hepatic cholesterol accumulation.
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah Erin.Zinkhan@hsc.utah.edu.
authors.forename: Erin K
authors.initials: EK
authors.lastname: Zinkhan
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 Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah.
authors.forename: Jeanette R
authors.initials: JR
authors.lastname: Carpenter
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: Xing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Gary
authors.initials: G
authors.lastname: Chan
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: D000367:Age Factors; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism* / Q000503:physiopathology; D007774:Lactation; D008099:Liver / Q000378:metabolism*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D011973:Receptors, LDL; D002784:Cholesterol
keywords: Cholesterol; Ldlr; intrauterine growth restriction; maternal high‐fat diet