Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Chandak, PG; Obrowsky, S; Radovic, B; Doddapattar, P; Aflaki, E; Kratzer, A; Doshi, LS; Povoden, S; Ahammer, H; Hoefler, G; Levak-Frank, S; Kratky, D.
Lack of acyl-CoA:diacylglycerol acyltransferase 1 reduces intestinal cholesterol absorption and attenuates atherosclerosis in apolipoprotein E knockout mice.
Biochim Biophys Acta. 2011; 1811(12): 1011-1020.
Doi: 10.1016/j.bbalip.2011.08.010
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- Führende Autor*innen der Med Uni Graz
- Chandak Prakash Gopal Das
- Kratky Dagmar
- Co-Autor*innen der Med Uni Graz
- Aflaki Elma
- Ahammer Helmut
- Doddapattar Prakash
- Doshi Lalitkumar Subhash
- Höfler Gerald
- Kratzer Adelheid
- Levak Sanja
- Obrowsky Sascha
- Radovic Branislav
- Rainer Silvia
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- Abstract:
- Triacylglycerols (TG) are the major storage molecules of metabolic energy and fatty acids in several tissues. The final step in TG biosynthesis is catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. Lack of whole body DGAT1 is associated with reduced lipid-induced inflammation. Since one major component of atherosclerosis is chronic inflammation we hypothesized that DGAT1 deficiency might ameliorate atherosclerotic lesion development. We therefore crossbred Apolipoprotein E-deficient (ApoE(-/-)) mice with Dgat1(-/-) mice. ApoE(-/-) and ApoE(-/-)Dgat1(-/-) mice were fed Western-type diet (WTD) for 9weeks and thereafter examined for plaque formation. The mean atherosclerotic lesion area was substantially reduced in ApoE(-/-)Dgat1(-/-) compared with ApoE(-/-) mice in en face and aortic valve section analyses. The reduced lesion size was associated with decreased cholesterol uptake and absorption by the intestine, reduced plasma TG and cholesterol concentrations and increased cholesterol efflux from macrophages. The expression of adhesion molecules was reduced in aortas of ApoE(-/-)Dgat1(-/-) mice, which might be the reason for less migration capacities of monocytes and macrophages and the observed decreased amount of macrophages within the plaques. From our results we conclude that the lack of DGAT1 is atheroprotective, implicating an additional application of DGAT1 inhibitors with regard to maintaining cholesterol homeostasis and attenuating atherosclerosis. Copyright © 2011 Elsevier B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Acyl Coenzyme A - blood
- Animals -
- Aorta - metabolism
- Apolipoproteins E - deficiency
- Atherosclerosis - blood
- Cell Movement - genetics
- Cells, Cultured -
- Cholesterol - blood
- Crosses, Genetic -
- Diacylglycerol O-Acyltransferase - deficiency
- Disease Models, Animal -
- Female -
- Humans -
- Immunohistochemistry -
- Intestinal Absorption - genetics
- Intestines - metabolism
- Lipid Metabolism - genetics
- Macrophages - cytology
- Mice -
- Mice, Knockout -
- Plaque, Atherosclerotic - blood
- Triglycerides - blood
- Find related publications in this database (Keywords)
- Atherosclerosis
- Cholesterol absorption
- Cholesterol efflux
- Acyl-CoA:diacylglycerol acyltransferase 1
- Inflammation
- Apolipoprotein E knockout mice