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

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

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)718-724
Number of pages7
JournalMetabolism: Clinical and Experimental
Volume57
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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