Journal of Lipid Research
Volume 44, Issue 11, November 2003, Pages 2109-2119
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Research Article
Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice

https://doi.org/10.1194/jlr.M300203-JLR200Get rights and content
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High-cholesterol diets elicit changes in gene expression via such transcription factors as sterol-regulatory element binding proteins (SREBPs) and liver X receptors (LXRs). We used Affymetrix microarrays to identify genes in mouse liver regulated by dietary cholesterol (0.0% vs. 0.5% cholesterol wt/wt). Three independent experiments were performed, and data were analyzed with Affymetrix Microarray Suite and ANOVA statistical software. There were 69 unique Unigene clusters consistently regulated by dietary cholesterol (37 downregulated and 32 upregulated). The array results were confirmed by quantitative RT-PCR (Q-PCR) for seven of nine downregulated genes and five of six upregulated genes. A time course of dietary cholesterol feeding over 1 week revealed different temporal patterns of gene regulation for these confirmed genes. Six downregulated genes were examined in transgenic mice overexpressing truncated nuclear forms of SREBP-1a and SREBP-2, and all were induced in these mice. A second microarray analysis of mice treated with the LXR agonist TO901317 confirmed that 13 of the 32 cholesterol upregulated genes were also LXR-activated. This array result was confirmed by Q-PCR for three of three genes.

In summary, these studies identified and confirmed six novel dietary cholesterol-regulated genes, three putative SREBP target genes (calcium/calmodulin-dependent protein kinase 1D, fatty acid binding protein 5, and proprotein convertase subtilisin/kexin 9), and three putative LXR target genes (a disintegrin and metalloprotease domain 11, apoptosis-inhibitory 6, and F-box-only protein 3).

dietary cholesterol
oligonucleotide arrays
gene expression profiling
sterol-regulatory element binding proteins
liver X receptor

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Published, JLR Papers in Press, August 1, 2003. DOI 10.1194/jlr.M300203-JLR200

    Abbreviations

    Abcg5

    ATP binding cassette, subfamily G, member 5

    Acac

    acetyl-CoA carboxylase

    Acly

    ATP citrate lyase

    Adam11

    a disintegrin and metalloprotease domain 11

    Api6

    apoptosis-inhibitory 6

    Camk1D

    calcium/calmodulin-dependent protein kinase 1D

    CYP7A1

    cholesterol 7-α-hydroxylase

    FABP5

    fatty acid binding protein 5

    Fbxo3

    F-box-only protein 3

    HMGCR

    HMG-CoA reductase

    HMGCS

    HMG-CoA synthase

    Laptm5

    lysosomal-associated protein transmembrane 5

    LXR

    liver X receptor

    Pcsk9

    proprotein convertase subtilisin/kexin 9

    Rgs16

    regulator of G-protein signaling 16

    SAA3

    serum amyloid A 3

    Sqle

    squalene epoxidase

    SREBP

    sterol-regulatory element binding protein

    StarD4

    StAR-related lipid transfer domain containing 4

The online version of this article (available at http://www.jlr.org) contains one supplemental table.