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: Erin K Zinkhan, Jennifer M Zalla, Jeanette R Carpenter, Baifeng Yu, Xing Yu, Gary Chan, Lisa Joss-Moore, Robert H Lane
• Journal: Physiological reports (Physiol Rep) Vol. 4 Issue 13 (Jul 2016) ISSN: 2051-817X [Print] United States
• PMID: 27401460 (Publication Type: Journal Article)
• Copyright: © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Chemical References

• Receptors, LDL
• Cholesterol

Topics

• Age Factors
• Animal Nutritional Physiological Phenomena
• Animals
• Cholesterol (metabolism)
• Diet, High-Fat
• Disease Models, Animal
• Female
• Fetal Growth Retardation (metabolism, physiopathology)
• Lactation
• Liver (metabolism)
• Male
• Maternal Nutritional Physiological Phenomena
• Pregnancy
• Prenatal Exposure Delayed Effects
• Rats, Sprague-Dawley
• Receptors, LDL (metabolism)
• Up-Regulation