Role of LXRs in control of lipogenesis

The discovery of oxysterols as the endogenous liver X receptor (LXR) ligands and subsequent gene targeting studies in mice provided strong evidence that LXR plays a central role in cholesterol metabolism. The identification here of a synthetic, nonsteroidal LXR-selective agonist series represented b...

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Bibliographic Details
Published in:Genes & development 2000-11, Vol.14 (22), p.2831-2838
Main Authors: Schultz, J R, Tu, H, Luk, A, Repa, J J, Medina, J C, Li, L, Schwendner, S, Wang, S, Thoolen, M, Mangelsdorf, D J, Lustig, K D, Shan, B
Format: Article
Language:English
Subjects:
Animals
CCAAT-Enhancer-Binding Proteins - metabolism
Cricetinae
DNA-Binding Proteins - metabolism
Dose-Response Relationship, Drug
Fatty Acids - biosynthesis
Hypertriglyceridemia - etiology
Lipids - biosynthesis
lipogenesis
Lipoproteins - blood
Liver - metabolism
Liver X Receptors
Mice
Mice, Mutant Strains
Orphan Nuclear Receptors
oxysterols
Phospholipids - blood
Receptors, Cytoplasmic and Nuclear - agonists
Research Paper
Sterol Regulatory Element Binding Protein 1
Sulfonamides - pharmacology
Transcription Factors
Triglycerides - blood
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Summary:The discovery of oxysterols as the endogenous liver X receptor (LXR) ligands and subsequent gene targeting studies in mice provided strong evidence that LXR plays a central role in cholesterol metabolism. The identification here of a synthetic, nonsteroidal LXR-selective agonist series represented by T0314407 and T0901317 revealed a novel physiological role of LXR. Oral administration of T0901317 to mice and hamsters showed that LXR activated the coordinate expression of major fatty acid biosynthetic genes (lipogenesis) and increased plasma triglyceride and phospholipid levels in both species. Complementary studies in cell culture and animals suggested that the increase in plasma lipids occurs via LXR-mediated induction of the sterol regulatory element-binding protein 1 (SREBP-1) lipogenic program.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.850400