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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kratzer, A; Buchebner, M; Pfeifer, T; Becker, TM; Uray, G; Miyazaki, M; Miyazaki-Anzai, S; Ebner, B; Chandak, PG; Kadam, RS; Calayir, E; Rathke, N; Ahammer, H; Radovic, B; Trauner, M; Hoefler, G; Kompella, UB; Fauler, G; Levi, M; Levak-Frank, S; Kostner, GM; Kratky, D.
Synthetic LXR agonist attenuates plaque formation in apoE-/- mice without inducing liver steatosis and hypertriglyceridemia.
J Lipid Res. 2009; 50(2): 312-326.
Doi: 10.1194/jlr.M800376-JLR200
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- Führende Autor*innen der Med Uni Graz
- Kratky Dagmar
- Kratzer Adelheid
- Co-Autor*innen der Med Uni Graz
- Ahammer Helmut
- Becker Tatjana
- Buchebner Marlene
- Chandak Prakash Gopal Das
- Fauler Günter
- Gallé Birgit
- Höfler Gerald
- Kostner Gerhard
- Levak Sanja
- Pfeifer Thomas
- Radovic Branislav
- Rathke Nora
- Trauner Michael
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- Abstract:
- Liver X receptors (LXRs) are important regulators of cholesterol and lipid metabolism. LXR agonists have been shown to limit the cellular cholesterol content by inducing reverse cholesterol transport, increasing bile acid production, and inhibiting intestinal cholesterol absorption. Most of them, however, also increase lipogenesis via sterol regulatory element-binding protein-1c (SREBP1c) and carbohydrate response element-binding protein activation resulting in hypertriglyceridemia and liver steatosis. We report on the antiatherogenic properties of the steroidal liver X receptor agonist N,N-dimethyl-3beta-hydroxy-cholenamide (DMHCA) in apolipoprotein E (apoE)-deficient mice. Long-term administration of DMHCA (11 weeks) significantly reduced lesion formation in male and female apoE-null mice. Notably, DMHCA neither increased hepatic triglyceride (TG) levels in male nor female apoE-deficient mice. ATP binding cassette transporter A1 and G1 and cholesterol 7alpha-hydroxylase mRNA abundances were increased, whereas SREBP1c mRNA expression was unchanged in liver, and even decreased in macrophages and intestine. Short-term treatment revealed even higher changes on mRNA regulation. Our data provide evidence that DMHCA is a strong candidate as therapeutic agent for the treatment or prevention of atherosclerosis, circumventing the negative side effects of other LXR agonists.
- Find related publications in this database (using NLM MeSH Indexing)
- ATP-Binding Cassette Transporters - genetics ATP-Binding Cassette Transporters - metabolism
- Animals -
- Apolipoproteins E - genetics Apolipoproteins E - metabolism
- Atherosclerosis - drug therapy Atherosclerosis - pathology
- Cholic Acids - therapeutic use
- DNA-Binding Proteins - agonists DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism
- Fatty Liver - chemically induced
- Female -
- Foam Cells - metabolism
- Hypertriglyceridemia - chemically induced
- Macrophages - metabolism
- Male -
- Mice -
- Mice, Inbred C57BL -
- Mice, Transgenic -
- Orphan Nuclear Receptors -
- RNA, Messenger - metabolism
- Receptors, Cytoplasmic and Nuclear - agonists Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - metabolism
- Sterol Regulatory Element Binding Protein 1 - genetics Sterol Regulatory Element Binding Protein 1 - metabolism
- Time Factors -
- Find related publications in this database (Keywords)
- atherogenesis
- liver X receptor
- cholesterol catabolism
- ABC transporter
- gene expression