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Cells 2018, 7(12), 264; https://doi.org/10.3390/cells7120264

Metabolic Signature of Dietary Iron Overload in a Mouse Model

1
Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
2
Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
3
Institute for Biomedicine, Eurac Research, Via Galvani 31, 39100 Bolzano, Italy
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 13 November 2018 / Revised: 3 December 2018 / Accepted: 7 December 2018 / Published: 11 December 2018
(This article belongs to the Special Issue Emerging Trends in Metal Biochemistry)
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Abstract

Iron is an essential co-factor for several metabolic processes, including the Krebs cycle and mitochondrial oxidative phosphorylation. Therefore, maintaining an appropriate iron balance is essential to ensure sufficient energy production and to avoid excessive reactive oxygen species formation. Iron overload impairs mitochondrial fitness; however, little is known about the associated metabolic changes. Here we aimed to characterize the metabolic signature triggered by dietary iron overload over time in a mouse model, where mice received either a standard or a high-iron diet. Metabolic profiling was assessed in blood, plasma and liver tissue. Peripheral blood was collected by means of volumetric absorptive microsampling (VAMS). Extracted blood and tissue metabolites were analyzed by liquid chromatography combined to high resolution mass spectrometry. Upon dietary iron loading we found increased glucose, aspartic acid and 2-/3-hydroxybutyric acid levels but low lactate and malate levels in peripheral blood and plasma, pointing to a re-programming of glucose homeostasis and the Krebs cycle. Further, iron loading resulted in the stimulation of the urea cycle in the liver. In addition, oxidative stress was enhanced in circulation and coincided with increased liver glutathione and systemic cysteine synthesis. Overall, iron supplementation affected several central metabolic circuits over time. Hence, in vivo investigation of metabolic signatures represents a novel and useful tool for getting deeper insights into iron-dependent regulatory circuits and for monitoring of patients with primary and secondary iron overload, and those ones receiving iron supplementation therapy. View Full-Text
Keywords: iron; metabolomics; VAMS; mitochondria; glucose; urea cycle; oxidative stress iron; metabolomics; VAMS; mitochondria; glucose; urea cycle; oxidative stress
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Volani, C.; Paglia, G.; Smarason, S.V.; Pramstaller, P.P.; Demetz, E.; Pfeifhofer-Obermair, C.; Weiss, G. Metabolic Signature of Dietary Iron Overload in a Mouse Model. Cells 2018, 7, 264.

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