Liver X receptors as insulin-mediating factors in fatty acid and cholesterol biosynthesis

Cholesterol Biosynthesis, Kari Anne Risan Tobin, Stine M. Ulven, Gertrud U. Schuster, Hilde Hermansen Steineger, Sissel Mæhle Andresen, Jan Åke Gustafsson, Hilde Irene Nebb

Research output: Contribution to journalArticle

151 Scopus citations

Abstract

The nuclear receptor liver X receptor (LXR) α, an important regulator of cholesterol and bile acid metabolism, was analyzed after insulin stimulation in liver in vitro and in vivo. A time- and dose-dependent increase in LXRα steady-state mRNA level was seen after insulin stimulation of primary rat hepatocytes in culture. A maximal induction of 10-fold was obtained when hepatocytes were exposed to 400 nM insulin for 24 h. Cycloheximide, a potent inhibitor of protein synthesis, prevented induction of LXRα mRNA expression by insulin, indicating that the induction is dependent on de novo synthesis of proteins. Stabilization studies using actinomycin D indicated that insulin stimulation increased the half-life of LXRα transcripts in cultured primary hepatocytes. Complementary studies where rats and mice were injected with insulin induced LXRα mRNA levels and confirmed our in vitro studies. Furthermore, deletion of both the LXRα and LXRβ genes (double knockout) in mice markedly suppressed insulin-mediated induction of an entire class of enzymes involved in both fatty acid and cholesterol metabolism. The discovery of insulin regulation of LXR in hepatic tissue as well as gene targeting studies in mice provide strong evidence that LXRs plays a central role not only in cholesterol homeostasis, but also in fatty acid metabolism. Furthermore, LXRs appear to be important insulin-mediating factors in regulation of lipogenesis.

Original languageEnglish (US)
Pages (from-to)10691-10697
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number12
DOIs
StatePublished - Mar 22 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Liver X receptors as insulin-mediating factors in fatty acid and cholesterol biosynthesis'. Together they form a unique fingerprint.

Cite this