期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
卷 1811, 期 12, 页码 1011-1020出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2011.08.010
关键词
Atherosclerosis; Cholesterol absorption; Cholesterol efflux; Acyl-CoA:diacylglycerol acyltransferase 1; Inflammation; Apolipoprotein E knockout mice
资金
- Austrian Science Fund [SFB-LIPOTOX F30, DK-MCD W1226, P19186, P22832]
- Austrian Federal Ministry of Science and Research
- Austrian Science Fund (FWF) [P22832] Funding Source: Austrian Science Fund (FWF)
- Austrian Science Fund (FWF) [F 3004, P 22832] Funding Source: researchfish
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 9 weeks and thereafter examined for plaque formation. The mean atherosclerotic lesion area was substantially reduced in ApoE(-/-)Dgat1(-/-) compared with ApoE(-/-) mice in enlace 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. (C) 2011 Elsevier B.V. All rights reserved.
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