Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2831-2838 |
| Number of pages | 8 |
| Journal | Genes and Development |
| Volume | 14 |
| Issue number | 22 |
| DOIs | |
| State | Published - Nov 15 2000 |
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Keywords
- Fatty acid
- Lipogenesis
- LXR
- SREBP
- Triglyceride
ASJC Scopus subject areas
- Genetics
- Developmental Biology
Cite this
Role of LXRs in control of lipogenesis. / Schultz, Joshua R.; Tu, Hua; Luk, Alvin; Repa, Joyce J.; Medina, Julio C.; Li, Leping; Schwendner, Susan; Wang, Shelley; Thoolen, Martin; Mangelsdorf, David J.; Lustig, Kevin D.; Shan, Bei.
In: Genes and Development, Vol. 14, No. 22, 15.11.2000, p. 2831-2838.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of LXRs in control of lipogenesis
AU - Schultz, Joshua R.
AU - Tu, Hua
AU - Luk, Alvin
AU - Repa, Joyce J.
AU - Medina, Julio C.
AU - Li, Leping
AU - Schwendner, Susan
AU - Wang, Shelley
AU - Thoolen, Martin
AU - Mangelsdorf, David J.
AU - Lustig, Kevin D.
AU - Shan, Bei
PY - 2000/11/15
Y1 - 2000/11/15
N2 - 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.
AB - 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.
KW - Fatty acid
KW - Lipogenesis
KW - LXR
KW - SREBP
KW - Triglyceride
UR - http://www.scopus.com/inward/record.url?scp=0034669171&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034669171&partnerID=8YFLogxK
U2 - 10.1101/gad.850400
DO - 10.1101/gad.850400
M3 - Article
VL - 14
SP - 2831
EP - 2838
JO - Genes and Development
JF - Genes and Development
SN - 0890-9369
IS - 22
ER -