Liver X receptors and cholesterol homoeostasis: Spotlight on the adrenal gland

C. L. Cummins, D. J. Mangelsdorf

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The LXRs (liver X receptors) (LXRα and LXRβ) are nuclear hormone receptors that are activated by oxysterols, endogenous oxidative metabolites of cholesterol. These receptors regulate an integrated network of genes that control whole body cholesterol and lipid homoeostasis. A brief overview of the mechanism of this regulation by LXRs in the liver, macrophage and intestine will be outlined, followed by data from our recent work demonstrating that LXRα is crucial in maintaining adrenal cholesterol homoeostasis. In the adrenal gland, oxysterols are formed as intermediates in the conversion of cholesterol into steroid hormones and can act as endogenous activators of LXR. We have found using both gain- and loss-of-function models that LXR acts to maintain free cholesterol below toxic levels in the adrenal gland, through the co-ordinated regulation of genes involved in cholesterol efflux [ABCA1 (ATP-binding-cassette transporter A1)], storage (sterol-regulatory-element- binding protein-1c and apolipoprotein E) and metabolism to steroid hormones (steroidogenic acute regulatory protein). Furthermore, we show that under chronic dietary stress, the adrenal glands of LXR-null mice (and not wild-type mice) accumulate free cholesterol. These results support the role of LXR as a global regulator of cholesterol homoeostasis, where LXR provides a safety valve to limit free cholesterol in tissues experiencing high cholesterol flux.

Original languageEnglish (US)
Pages (from-to)1110-1113
Number of pages4
JournalBiochemical Society Transactions
Volume34
Issue number6
DOIs
StatePublished - 2006

Keywords

  • Adrenal gland
  • Cholesterol
  • Corticosterone
  • Lipid metabolism
  • Liver X receptor (LXR)
  • Nuclear receptor

ASJC Scopus subject areas

  • Biochemistry

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