Accumulation of foam cells in liver X receptor-deficient mice.
BACKGROUND
The nature of some of the target genes for liver X receptors (LXRs)-alpha and -beta, 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.


RESULTS
Mice depleted for LXRalpha, LXRbeta, or both were fed low-fat rodent chow for 18 months before investigations. The combined deficiency of LXRalpha and LXRbeta 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.
Department of Biosciences at Novum, Karolinska Institutet, Huddinge, Sweden. gertrud.schuster@csb.ki.se
Gertrud U
GU
Schuster
Paolo
P
Parini
Ling
L
Wang
Siegfried
S
Alberti
Knut R
KR
Steffensen
Göran K
GK
Hansson
Bo
B
Angelin
Jan-Ake
JA
Gustafsson
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D000375:Aging / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats; D005487:Foam Cells / Q000166:cytology* / Q000378:metabolism*; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D000071518:Liver X Receptors; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency* / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000172:deficiency* / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000172:deficiency* / Q000235:genetics; D013154:Spleen / Q000473:pathology; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D022762:CCAAT-Enhancer-Binding Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004268:DNA-Binding Proteins; D004041:Dietary Fats; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011973:Receptors, LDL; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C497388:Srebf1 protein, mouse; C497391:Srebf2 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D014280:Triglycerides; D002784:Cholesterol