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SHR Neuro Krebs Kardio Lipid

Sachdev, V; Leopold, C; Bauer, R; Patankar, JV; Iqbal, J; Obrowsky, S; Boverhof, R; Doktorova, M; Scheicher, B; Goeritzer, M; Kolb, D; Turnbull, AV; Zimmer, A; Hoefler, G; Hussain, MM; Groen, AK; Kratky, D.
Novel role of a triglyceride-synthesizing enzyme: DGAT1 at the crossroad between triglyceride and cholesterol metabolism.
Biochim Biophys Acta. 2016; 1861(9 Pt A):1132-1141 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Bauer Raimund
Göritzer Madeleine
Hoefler Gerald
Kolb-Lenz Dagmar
Kratky Dagmar
Leopold Christina
Obrowsky Sascha
Patankar Jay Vasant
Sachdev Vinay
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Number of Figures: 6
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Abstract:
Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in triacylglycerol (TG) biosynthesis. Here we show that genetic deficiency and pharmacological inhibition of DGAT1 in mice alters cholesterol metabolism. Cholesterol absorption, as assessed by acute cholesterol uptake, was significantly decreased in the small intestine and liver upon DGAT1 deficiency/inhibition. Ablation of DGAT1 in the intestine (I-DGAT1(-/-)) alone is sufficient to cause these effects. Consequences of I-DGAT1 deficiency phenocopy findings in whole-body DGAT1(-/-) and DGAT1 inhibitor-treated mice. We show that deficiency/inhibition of DGAT1 affects cholesterol metabolism via reduced chylomicron size and increased trans-intestinal cholesterol excretion. These effects are independent of cholesterol uptake at the apical surface of enterocytes but mediated through altered dietary fatty acid metabolism. Our findings provide insight into a novel role of DGAT1 and identify a pathway by which intestinal DGAT1 deficiency affects whole-body cholesterol homeostasis in mice. Targeting intestinal DGAT1 may represent a novel approach for treating hypercholesterolemia. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Find related publications in this database (Keywords)
Cholesterol absorption
Chylomicron size
DGAT1 inhibition
Intestinal DGAT1 deficiency
Trans-intestinal cholesterol excretion
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