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Role of LXRs in control of lipogenesis
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.
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LXRs are critical for maximal transcription of SREBP-1c.
“LXRs are critical for maximal transcription of SREBP-1c, and loss of hepatic LXR expression therefore compromises SREBP-1c-dependent lipogenesis (DeBose-Boyd et al., 2001; Repa et al., 2000a; Schultz et al., 2000).”
From Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP (2017) · cites this paper as Schultz et al., 2000
Loss of hepatic LXR expression compromises SREBP-1c-dependent lipogenesis.
“LXRs are critical for maximal transcription of SREBP-1c, and loss of hepatic LXR expression therefore compromises SREBP-1c-dependent lipogenesis (DeBose-Boyd et al., 2001; Repa et al., 2000a; Schultz et al., 2000).”
From Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP (2017) · cites this paper as Schultz et al., 2000
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Metadata
- 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.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2000-11-15
- Volume
- 14
- Issue
- 22
- Pages
- 2831-2838
- ISSN
- 0890-9369
- 1549-5477
- Cited by
- 1,499
- References
- 4
- Language
- en
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