Published Online
on August 5, 2002

A more recent version of this article appeared on August 27, 2002

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Submitted on May 29, 2002
Accepted on June 3, 2002

Accumulation of Foam Cells in Liver X Receptor--Deficient Mice

Gertrud U. Schuster PhD^*, Paolo Parini MD, PhD, Ling Wang MD, PhD, Siegfried Alberti PhD, Knut R. Steffensen MSc, Göran K. Hansson MD, PhD, Bo Angelin MD, PhD, and Jan-Åke Gustafsson MD, PhD

From the Department of Biosciences at Novum, Karolinska Institutet (G.U.S., P.P., L.W., S.A., K.R.S., B.A., J.G.), Huddinge, Sweden; Metabolism Unit, Center for Metabolism and Endocrinology, Department of Medicine, Karolinska Institutet at Huddinge University Hospital (P.P., B.A.), Stockholm, Sweden; and Center for Molecular Medicine, Karolinska Institutet at Karolinska Hospital (G.K.H.), Stockholm, Sweden. Dr Alberti is now at the University of Tübingen, Institute for Cell Biology, Department of Molecular Biology, Tübingen, Germany.

^* To whom correspondence should be addressed. E-mail: gertrud.schuster{at}csb.ki.se.

Background—The nature of some of the target genes for liver X receptors (LXRs)- and -ß, such as sterol regulatory element binding protein-1 and ATP-binding cassette transporter proteins, suggests a pivotal role of these nuclear receptors in the regulation of fatty acid and cholesterol homeostasis. The present study aimed to elucidate the physiological relevance of both LXRs with regard to lipid metabolism and macrophage cholesterol efflux.

Methods and Results—Mice depleted for LXR, LXRß, or both were fed low-fat rodent chow for 18 months before investigations. The combined deficiency of LXR and LXRß was linked to impaired triglyceride metabolism, increased LDL and reduced HDL cholesterol levels, and cholesterol accumulation in macrophages (foam cells) of the spleen, lung, and arterial wall.

Conclusions—Our data demonstrate the physiological importance of both LXRs in lipid metabolism and strongly indicate that both LXRs have a protective role against the development of atherosclerosis.

Key words: receptors, liver X • atherosclerosis • lipoproteins • fatty acids • cholesterol

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