Anti-NR1H2 monoclonal antibody

Defining complete sets of gene family members from diverse species provides the foundation for comparative studies. Using a bioinformatic approach, we have defined the entire nuclear receptor complement within the first available complete sequence of a non-human vertebrate (the teleost fish Fugu rubripes). In contrast to the human set (48 total nuclear receptors), we found 68 nuclear receptors in the Fugu genome. All 68 Fugu receptors had a clear human homolog, thus defining no new nuclear receptor subgroups. A reciprocal analysis showed that each human receptor had one or more Fugu orthologs, excepting CAR (NR1I3) and LXRbeta (NR1H2). These 68 receptors add striking diversity to the known nuclear receptor superfamily and provide important comparators to human nuclear receptors. We have compared several pharmacologically relevant human nuclear receptors (FXR, LXRalpha/beta, CAR, PXR, VDR and PPARalpha/gamma/delta) to their Fugu orthologs. This comparison included expression analysis across five Fugu tissue types. All of the Fugu receptors that were analyzed by PCR in this study were expressed, indicating that the majority of the additional Fugu receptors are likely to be functional.

Liver X Receptor-alpha (LXR alpha also known as NR1H3) and LXR beta (NR1H2) are members of the nuclear receptor superfamily of ligand-activated transcription factors, a superfamily which includes the more widely known glucocorticoid receptor, estrogen receptor, thyroid receptor, and peroxisome proliferator-activated receptors. The LXRs are activated by physiologic sterol ligands (e. g., oxysterols) and by synthetic agonists. In recent years, our understanding of the importance of LXRs has expanded across several fields of (patho-) physiology. Perhaps best known from a sizeable literature as homeostatic 'cholesterol sensors' that drive transcriptional programs promoting cellular cholesterol efflux, 'reverse cholesterol transport,' and bile acid synthesis, more recent roles for LXRs in glucose homeostasis, atherosclerosis, and innate immunity have also been identified. These discoveries complement an emerging literature that continues to draw surprisingly intimate connections between host metabolism and host defense. The present review will discuss the roles of LXR in the signaling of metabolism and innate immunity, and the potential for synthetic LXR agonists as novel therapeutics in dyslipidemia, atherosclerosis, disordered glucose metabolism, and inflammation.