Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Doi: 10.1016/j.bbalip.2016.06.014
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- Führende Autor*innen der Med Uni Graz
- Kratky Dagmar
- Sachdev Vinay
- Co-Autor*innen der Med Uni Graz
- Bauer Raimund
- Göritzer Madeleine
- Höfler Gerald
- Kolb Dagmar
- Leopold Christina
- Obrowsky Sascha
- Patankar Jay Vasant
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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 (using NLM MeSH Indexing)
- Animals -
- Cholesterol - metabolism
- Diacylglycerol O-Acyltransferase - deficiency
- Diacylglycerol O-Acyltransferase - genetics
- Diacylglycerol O-Acyltransferase - metabolism
- Dietary Fats -
- Fatty Acids - metabolism
- Hypercholesterolemia - drug therapy
- Hypercholesterolemia - metabolism
- Intestinal Absorption - genetics
- Lipid Metabolism - genetics
- Lipogenesis - genetics
- Liver - metabolism
- Mice -
- Triglycerides - metabolism
- Find related publications in this database (Keywords)
- Cholesterol absorption
- Chylomicron size
- DGAT1 inhibition
- Intestinal DGAT1 deficiency
- Trans-intestinal cholesterol excretion