The nuclear receptors liver X receptors (LXR) alpha and beta are important regulators of genes involved in lipid, cholesterol, and carbohydrate metabolism and are highly expressed in mature adipocyte tissue. In this study we show that LXRalpha and LXRbeta are more expressed in brown adipose tissue and subcutaneous white adipose tissue than visceral (gonadal) adipose tissue. Furthermore, we report differences between LXRalpha and LXRbeta in their ability to alter expression of target genes. Gene expression profiling analysis of gonadal white adipose tissue from LXRalpha(-/-) mice and LXRbeta(-/-) mice shows different gene expression patterns in the two LXR-deficient mouse strains. Genes regulated similarly in both KO mouse strains as well as genes regulated in one, but not the other LXR-deficient mouse strain were seen. A number of genes were regulated in opposite directions by the respective LXR isoform. Taken together this suggests that the LXR isoforms might operate through different transcriptional mechanisms as well as common mechanisms. These results are in consonance with the growing body of evidence reporting differences in regulation of gene expression between the two isoforms. Furthermore, gene expression profiling shows altered gene expression patterns in primary mouse embryonic fibroblasts (MEFs) from wild type versus LXRbeta(-/-) mice; MEFs are pluripotent cells with the potential to differentiate into mature adipocytes. These results indicate a role of LXR in early developmental stages of adipose tissue. (C) 2003 Elsevier Inc. All rights reserved.