Naslov
Activation of liver x receptors in the brain: regulation of target gene expression without disturbing steady-state lipid homeostasis

Autori
Štefulj, Jasminka ; Schweinzer, C. ; Reicher, H. ; Calayir, E. ; Kratzer, A. ; Sattler, W. ; Panzenboeck, U

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Journal of Clinical Lipidology / Brown, Virgil - New York (NY) : Elsevier, 2007, 459-459

Skup
XVI International Symposium on drugs affecting lipid metabolism

Mjesto i datum
Sjedinjene Američke Države, 04.10.2007. - 07.10.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
cholesterol ; brain ; LXR

Sažetak
Objective: The present study was aimed at clarifying the impact of in vivo activation of LXRs on the brain lipid metabolism. Methods: C57Bl6 mice were treated orally with vehicle or TO901317, a synthetic LXR agonist which crosses the blood-brain barrier. Ex-vivo analyses included brain expression of the relevant genes (qRT-PCR, western blot), as well as brain and plasma lipid composition (HPLC, GC-MS). Results: Expression analysis revealed elevated levels of Abca1 and Abcg1 in the brains of TO901317 treated mice as compared to mice treated with vehicle, but decreased levels of SR-BI and no changes in the Abcg4 expression. Administration of TO901317 resulted also in increased brain expression of Apo-AI and ApoE, while no changes were observed in the expression of Cyp46a1, Lipg, Lpl, NPC2 and APP. Interestingly, Pltp expression in the brain appeared to be down-regulated by TO901317, and moreover, negatively correlated with brain ApoE and liver Pltp expression. Similarly, negative correlation was observed between APP and Abcg1 expression in the brain. Analysis of plasma lipid composition demonstrated elevated levels of total cholesterol, HDL-cholesterol and phospholipids in TO901317 treated mice versus mice receiving vehicle. Despite alternations in plasma lipid composition and in brain expression of genes involved in cholesterol turnover, no changes were observed in the brain levels of cholesterol, a-tocopherol and total fatty acids. Conclusions: Obtained results suggest that LXR activation in vivo promotes cholesterol recycling in the brain, without disturbing cerebral steady-state lipid homeostasis.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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