T-0901317, a synthetic liver X receptor ligand, inhibits development of atherosclerosis in LDL receptor-deficient mice

FEBS Lett. 2003 Feb 11;536(1-3):6-11. doi: 10.1016/s0014-5793(02)03578-0.


Liver X receptors (LXR alpha and LXR beta) are nuclear receptors, which are important regulators of cholesterol and lipid metabolism. LXRs control genes involved in cholesterol efflux in macrophages, bile acid synthesis in liver and intestinal cholesterol absorption. LXRs also regulate genes participating in lipogenesis. To determine whether the activation of LXR promotes or inhibits development of atherosclerosis, T-0901317, a synthetic LXR ligand, was administered to low density lipoprotein receptor (LDLR)(-/-) mice. T-0901317 significantly reduced the atherosclerotic lesions in LDLR(-/-) mice without affecting plasma total cholesterol levels. This anti-atherogenic effect correlated with the plasma concentration of T-0901317, but not with high density lipoprotein cholesterol, which was increased by T-0901317. In addition, we observed that T-0901317 increased expression of ATP binding cassette A1 in the lesions in LDLR(-/-) mice as well as in mouse peritoneal macrophages. T-0901317 also significantly induced cholesterol efflux activity in peritoneal macrophages. These results suggest that LXR ligands may be useful therapeutic agents for the treatment of atherosclerosis.

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / biosynthesis
  • ATP-Binding Cassette Transporters / genetics
  • Animals
  • Anticholesteremic Agents / therapeutic use*
  • Arteriosclerosis / metabolism
  • Arteriosclerosis / pathology
  • Arteriosclerosis / prevention & control*
  • Biological Transport
  • Cholesterol / metabolism
  • DNA-Binding Proteins
  • Hydrocarbons, Fluorinated
  • Ligands
  • Lipids / blood
  • Lipoproteins / blood
  • Liver X Receptors
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Orphan Nuclear Receptors
  • RNA, Messenger / biosynthesis
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, LDL / genetics
  • Sulfonamides


  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Anticholesteremic Agents
  • DNA-Binding Proteins
  • Hydrocarbons, Fluorinated
  • Ligands
  • Lipids
  • Lipoproteins
  • Liver X Receptors
  • Nr1h3 protein, mouse
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, LDL
  • Sulfonamides
  • TO-901317
  • Cholesterol