Submitted on December 6, 2005
Accepted on April 12, 2006
Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice
Paul A Dawson1, Brooke Gardiner2, Sean Grimmond3, and Daniel Markovich1*
1 School of Biomedical Sciences, University of Queensland, Brisbane, Australia
2 Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
3 University of Queensland, Institute for Molecular Bioscience, St Lucia, Australia
* To whom correspondence should be addressed. E-mail: d.markovich{at}uq.edu.au.
Sulfate plays an essential role in human growth and development, and its circulating levels are maintained by the renal Na+-SO42- cotransporter, NaS1. We previously generated a NaS1 knock-out (N
s1-/-) mouse, an animal model for hyposulfatemia, which exhibits reduced growth and liver abnormalities, including hepatomegaly. In this study, we investigated the hepatic gene expression profile of Ns1-/- mice using oligonucleotide microarrays. The mRNA expression level of 92 genes with known functional roles in metabolism, cell signaling, cell defense, immune response, cell structure, transcription or protein synthesis, were increased (n=51) or decreased (n=41) in Ns1-/- mice when compared with Ns1+/+ mice. The most up-regulated transcript levels in Ns1-/- mice were found for the sulfotransferase genes, Sult31 (
500% increase) and Sult22 (100% increase), whereas the metallothionein-1 gene, Mt1, was amongst the most down-regulated genes (70% decrease). Several genes involved in lipid and cholesterol metabolism, including Scd1, Acly, Gpm, Elov16, Acsl5, Mvd, Insig1 and Apo4, were found to be up-regulated (
30% increase) in Ns1-/- mice. In addition, Ns1-/- mice exhibited increased levels of hepatic lipid (16% increase), serum cholesterol (20% increase) and LDL (100% increase), and reduced hepatic glycogen (50% decrease) levels. In conclusion, these data suggest an altered lipid and cholesterol metabolism in the hyposulfatemic Ns1-/- mouse, and provide new insights into the metabolic state of the liver in Ns1-/- mice.
