Regulation of Lipoprotein Lipase by the Oxysterol Receptors, LXRα and LXRβ

Yuan Zhang, Joyce J. Repa, Karine Gauthier, David J. Mangelsdorf

Research output: Contribution to journalArticle

232 Scopus citations

Abstract

Lipoprotein lipase (LPL) is a key enzyme for lipoprotein metabolism and is responsible for hydrolysis of triglycerides in circulating lipoproteins, releasing free fatty acids to peripheral tissues. In liver, LPL is also believed to promote uptake of high density lipoprotein (HDL)-cholesterol and thereby facilitate reverse cholesterol transport. In this study we show that the Lpl gene is a direct target of the oxysterol liver X receptor, LXRα. Mice fed diets containing high cholesterol or an LXR-selective agonist exhibited a significant increase in LPL expression in the liver and macrophages, but not in other tissues (e.g. adipose and muscle). Studies in Lxr-deficient mice confirmed that this response was dependent more on the presence of LXRα than LXRβ. Analysis of the Lpl gene revealed the presence of a functional DR4 LXR response element in the intronic region between exons 1 and 2. This response element directly binds rexinoid receptor (RXR)/LXR heterodimers and is sufficient for rexinoid- and LXR agonist-induced transcription of the Lpl gene. Together, these studies further distinguish the roles of LXRα and β and support a growing body of evidence that LXRs function as key regulators of lipid metabolism and are anti-atherogenic.

Original languageEnglish (US)
Pages (from-to)43018-43024
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number46
DOIs
StatePublished - Nov 16 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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