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Tryptophan depletion under conditions that imitate insulin resistance enhances fatty acid oxidation and induces endothelial dysfunction through reactive oxygen species-dependent and independent pathways

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A Correction to this article was published on 24 January 2018

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Abstract

In atherosclerosis-associated pathologic entities characterized by malnutrition and inflammation, l-tryptophan (TRP) levels are low. Insulin resistance is an independent cardiovascular risk factor and induces endothelial dysfunction by increasing fatty acid oxidation. It is also associated with inflammation and low TRP levels. Low TRP levels have been related to worse cardiovascular outcome. This study evaluated the effect of TRP depletion on endothelial dysfunction under conditions that imitate insulin resistance. Fatty acid oxidation, harmful pathways due to increased fatty acid oxidation, and endothelial dysfunction were assessed in primary human aortic endothelial cells cultured under normal glucose, low insulin conditions in the presence or absence of TRP. TRP depletion activated general control non-derepressible 2 kinase and inhibited aryl hydrocarbon receptor. It increased fatty acid oxidation by increasing expression and activity of carnitine palmitoyltransferase 1. Elevated fatty acid oxidation increased the formation of reactive oxygen species (ROS) triggering the polyol and hexosamine pathways, and enhancing protein kinase C activity and methylglyoxal production. TRP absence inhibited nitric oxide synthase activity in a ROS-dependent way, whereas it increased the expression of ICAM-1 and VCAM-1 in a ROS independent and possibly p53-dependent manner. Thus, TRP depletion, an amino acid whose low levels have been related to worse cardiovascular outcome and to inflammatory atherosclerosis-associated pathologic entities, under conditions that imitate insulin resistance enhances fatty acid oxidation and induces endothelial dysfunction through ROS-dependent and independent pathways. These findings may offer new insights at the molecular mechanisms involved in accelerated atherosclerosis that frequently accompanies malnutrition and inflammation.

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  • 24 January 2018

    In the original publication of the article, last author’s name was misspelt. The correct name is given here.

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  1. Department of Nephrology, Medical School, University of Thessaly, Neo Ktirio, Mezourlo Hill, 41110, Larissa, Greece

    Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Georgia Antoniadi, Vassilios Liakopoulos & loannis Stefanidis

  2. Department of Interventional Radiology, Medical School, University of Thessaly, Larissa, Greece

    Christos Rountas

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  1. Theodoros Eleftheriadis
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Eleftheriadis, T., Pissas, G., Sounidaki, M. et al. Tryptophan depletion under conditions that imitate insulin resistance enhances fatty acid oxidation and induces endothelial dysfunction through reactive oxygen species-dependent and independent pathways. Mol Cell Biochem 428, 41–56 (2017). https://doi.org/10.1007/s11010-016-2915-7

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