Influence of liver-X-receptor on tissue cholesterol, coenzyme Q and dolichol content.
The organ content of the mevalonate pathway lipids was investigated in liver-X-receptor (LXR) α, β and double knock-out mice. An extensive or moderate increase of total cholesterol in the double KO mice was found in all organs elicited by the increase of the esterified form. In LXRα and double KO mice, coenzyme Q (CoQ) was decreased in liver and increased in spleen, thymus and lung, while dolichol was increased in all organs investigated. This effect was confirmed using LXR- agonist GW 3965. Analysis of CoQ distribution in organelles showed that the modifications are present in all cellular compartments and that the increase of the lipid in mitochondria was the result of a net increase of CoQ without changing the number of mitochondria. It appears that LXR influences not only cellular cholesterol homeostasis but also the metabolism of CoQ and dolichol, in an indirect manner.
Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
Magnus
M
Bentinger
Michael
M
Tekle
Gustav
G
Dallner
Kerstin
K
Brismar
Jan-Åke
JÅ
Gustafsson
Knut R
KR
Steffensen
Sergiu-Bogdan
SB
Catrina
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D004286:Dolichols / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors; D008168:Lung / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity / Q000502:physiology; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism; D014451:Ubiquinone / Q000235:genetics / Q000378:metabolism*
D001565:Benzoates; D001596:Benzylamines; D004286:Dolichols; C473027:GW 3965; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D014451:Ubiquinone; D002784:Cholesterol