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Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism.
Stechemesser, L; Eder, SK; Wagner, A; Patsch, W; Feldman, A; Strasser, M; Auer, S; Niederseer, D; Huber-Schönauer, U; Paulweber, B; Zandanell, S; Ruhaltinger, S; Weghuber, D; Haschke-Becher, E; Grabmer, C; Rohde, E; Datz, C; Felder, TK; Aigner, E;
Mol Metab. 2017; 6(1):38-47
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Aigner Elmar
Auer Simon
Eder Sebastian
Felder Thomas
Feldman Alexandra
Grabmer Christoph
Haschke-Becher Elisabeth
Patsch Wolfgang
Paulweber Bernhard
Rohde Eva
Stechemesser Lars
Strasser Michael
Wagner Andrej
Weghuber Daniel
Zandanell Stephan

Abstract

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.
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.
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).
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.


Useful keywords (using NLM MeSH Indexing)

Adult

Blood Glucose/metabolism

Citrulline/blood

Citrulline/metabolism

Cross-Sectional Studies

Diabetes Mellitus, Type 2/metabolism

Female

Ferritins/analysis

Ferritins/blood

Ferritins/metabolism

Glucose/metabolism*

Glucose Tolerance Test

Homeostasis

Humans

Insulin Resistance/physiology

Iron/blood

Iron/metabolism*

Male

Metabolic Syndrome/metabolism

Metabolomics/methods

Middle Aged

Obesity/blood

Sarcosine/blood

Sarcosine/metabolism


Find related publications in this database (Keywords)

Metabolomics
Hyperferritinemia
Iron overload
Metabolic syndrome
Glucose