Liver X receptor

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Liver X receptors (LXR) are a family of ligand-activated transcription factors originally characterised in studies of lipid metabolic signaling and now realised to be important in conditions as diverse as nervous system development, oncology and thrombosis. As well as regulating cholesterol and fatty acid homeostasis they have other physiological functions including glucose homeostasis, immunological, and neuroprotective[1]. They are the nuclear receptor target of oxysterols, the oxidized forms of cholesterol, and several steroid analogues have been developed as agonists. There are two distinct genes that code for:

  1. Oxysterols receptor LXR-alpha (LXRalpha, LXRα)
    • Coded by NR1H3 gene at 11p11.2
    • Highly expressed in the liver, adipose, kidney, adrenal tissues, and macrophages
  2. Oxysterols receptor LXR-beta - (LXRbeta, LXRβ)
    • Coded by NR1H2 gene at 19q13.3
    • Ubiquitously expressed

In lipid metabolism they can be regarded as cholesterol sensors that:

  1. Lower cholesterol levels by increasing expression of genes associated with reverse cholesterol transport, bile acid formation and intestinal cholesterol absorption.
  2. Increase fatty acid and triglyceride synthesis

LXR agonists include:

  • N,N-dimethyl-3β-hydroxy-cholenamide (DMHCA)
  • 22(R)-hydroxycholesterol
  • 24(S)-hydroxycholesterol

References

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