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Vol. 62, Issue 6, 1299-1305, December 2002
Department of Medical Nutrition and Biosciences, Karolinska
Institutet, Huddinge, Sweden (T.M.S., K.R.S., H.G., K. D.-W.,
G.U.S., J.-Å.G.); and the Center for Genomics and Bioinformatics,
Karolinska Institutet, Stockholm, Sweden (M.R.)
Liver X receptor (LXR) 
and LXR
are nuclear oxysterol receptors
whose biological function has so far been elucidated only with respect
to cholesterol and lipid metabolism. To expose novel biological roles
for LXRs, we performed genome-wide gene expression profiling studies in
liver and white and brown adipose tissue from wild-type
(LXR+/++/+) and knockout mice
(LXR
//) treated with a synthetic
LXR agonist. By an adapted statistical analysis, we detected 319 genes
significantly regulated by LXR agonist treatment in wild-type but not
in knockout mice, fulfilling most stringent criteria with an overall
confidence of 94%. Down-regulation of essential enzymes of
gluconeogenesis in liver could point to possible beneficial effects of
LXR agonists in diabetes mellitus. LXR agonist treatment also altered
expression of genes involved in steroid hormone synthesis and growth
hormone receptor signaling, emphasizing a potential impact on endocrine
function. Notably, LXR agonist treatment up-regulated CYP4A10 and
CYP4A14 together with cytochrome P450 reductase, indicating a possible
enhancement of microsomal lipid peroxidation. In conclusion, these gene
expression profiling data identify novel areas of regulation by LXRs
and provide a highly valuable basis for further research on the
biological functions of these nuclear receptors and the pharmacological
characteristics of their ligands.
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