Role of LXRs in control of lipogenesis

Joshua R. Schultz, Hua Tu, Alvin Luk, Joyce J. Repa, Julio C. Medina, Leping Li, Susan Schwendner, Shelley Wang, Martin Thoolen, David J. Mangelsdorf, Kevin D. Lustig, Bei Shan

Research output: Contribution to journalArticle

1235 Scopus citations

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 languageEnglish (US)
Pages (from-to)2831-2838
Number of pages8
JournalGenes and Development
Volume14
Issue number22
DOIs
Publication statusPublished - Nov 15 2000

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Keywords

  • Fatty acid
  • Lipogenesis
  • LXR
  • SREBP
  • Triglyceride

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Schultz, J. R., Tu, H., Luk, A., Repa, J. J., Medina, J. C., Li, L., ... Shan, B. (2000). Role of LXRs in control of lipogenesis. Genes and Development, 14(22), 2831-2838. https://doi.org/10.1101/gad.850400