Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

• Main Authors: Lars Stechemesser, Sebastian K. Eder, Andrej Wagner, Wolfgang Patsch, Alexandra Feldman, Michael Strasser, Simon Auer, David Niederseer, Ursula Huber-Schönauer, Bernhard Paulweber, Stephan Zandanell, Sandra Ruhaltinger, Daniel Weghuber, Elisabeth Haschke-Becher, Christoph Grabmer, Eva Rohde, Christian Datz, Thomas K. Felder, Elmar Aigner
• Format: Article
• Language: English
• Published: Elsevier 2017-01-01
• Series: Molecular Metabolism
• Online Access: http://www.sciencedirect.com/science/article/pii/S2212877816302095

Objective: Elevated serum ferritin has been linked to type 2 diabetes (T2D) and adverse health outcomes in subjects with the Metabolic Syndrome (MetS). As the mechanisms underlying the negative impact of excess iron have so far remained elusive, we aimed to identify potential links between iron homeostasis and metabolic pathways. Methods: In a cross-sectional study, data were obtained from 163 patients, allocated to one of three groups: (1) lean, healthy controls (n = 53), (2) MetS without hyperferritinemia (n = 54) and (3) MetS with hyperferritinemia (n = 56). An additional phlebotomy study included 29 patients with biopsy-proven iron overload before and after iron removal. A detailed clinical and biochemical characterization was obtained and metabolomic profiling was performed via a targeted metabolomics approach. Results: Subjects with MetS and elevated ferritin had higher fasting glucose (p < 0.001), HbA1c (p = 0.035) and 1 h glucose in oral glucose tolerance test (p = 0.002) compared to MetS subjects without iron overload, whereas other clinical and biochemical features of the MetS were not different. The metabolomic study revealed significant differences between MetS with high and low ferritin in the serum concentrations of sarcosine, citrulline and particularly long-chain phosphatidylcholines. Methionine, glutamate, and long-chain phosphatidylcholines were significantly different before and after phlebotomy (p < 0.05 for all metabolites). Conclusions: Our data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism. Author Video: Author Video Watch what authors say about their articles Keywords: Metabolomics, Hyperferritinemia, Iron overload, Metabolic syndrome, Glucose