Differential expression of hepatic genes involved in cholesterol homeostasis in high- and low-responding strains of laboratory opossums

Chan, Jeannie; Donalson, Lisa M.; Kushwaha, Rampratap S.; Ferdinandusse, Sacha; VandeBerg, Jane F.; VandeBerg, John L.

doi:10.1016/j.metabol.2008.01.018

« PreviousMetabolism - Clinical and Experimental
Volume 57, Issue 5 , Pages 718-724, May 2008

Differential expression of hepatic genes involved in cholesterol homeostasis in high- and low-responding strains of laboratory opossums

Jeannie Chan
- Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549, USA
- Department of Genetics, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549, USA
- Corresponding author. Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549, USA. Tel.: +1 210 258 9745; fax: +1 210 258 9883.
Lisa M. Donalson
- Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549, USA
- Department of Genetics, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549, USA
Rampratap S. Kushwaha
- Department of Physiology and Medicine, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549, USA
Sacha Ferdinandusse
- Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Jane F. VandeBerg
- Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549, USA
- Department of Genetics, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549, USA
John L. VandeBerg
- Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549, USA
- Department of Genetics, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549, USA

Received 13 September 2007; accepted 7 January 2008.

Abstract

Plasma very low-density lipoprotein and low-density lipoprotein (VLDL + LDL) cholesterol levels of 2 partially inbred strains of opossums (Monodelphis domestica) differ markedly when they are fed a high-cholesterol and low-fat (HCLF) diet. High-responding opossums exhibit a dramatic increase (>10-fold) in VLDL + LDL cholesterol, whereas low-responding opossums exhibit a minimal increase (<2-fold) in VLDL + LDL cholesterol. The genes responsible for the accumulation of high levels of plasma VLDL + LDL cholesterol in high-responding opossums have not yet been identified. In this study, we analyzed the expression of genes encoding for (1) 4 bile acid synthesis enzymes (CYP7A1, CYP27A1, CYP8B1, and CYP7B1); (2) 3 cholesterol synthesis enzymes (HMGCR, HMGCS1, and SQLE); (3) the LDL receptor (LDLR); (4) 2 sterol transporters (ABCG5 and ABCG8); and (5) 2 bile acid transporters (ABCB11 and SLC10A1) to determine how the expression of these genes was affected by dietary cholesterol in the 2 strains of opossums. We found differences between high and low responders in the expression of cholesterol synthesis genes on the basal diet, as well as differences in the expression of the CYP27A1, ABCG5, ABCG8, and SLC10A1 genes on the HCLF diet. CYP27A1 messenger RNA levels were lower in the livers of high responders compared with low responders, whereas CYP27A1 messenger RNA levels in extrahepatic tissues were similar in high and low responders on the HCLF diet. Low levels of CYP27A1, ABCG5, and ABCG8 expression in the liver may contribute to hypercholesterolemia in high-responding opossums.