ECE2018 Poster Presentations: Thyroid Thyroid (non-cancer) (105 abstracts)
A thyroid hormone-independent molecular fingerprint of 3,5-diiodothyronine suggests a strong relation with coffee metabolism in humans
Maik Pietzner 1, , Georg Homuth 3 , Josef Köhrle 4 , Kathrin Budde 1, , Gabi Kastenmüller 5 , Georg Brabant 6 , Henry Völzke 2, , Anna Artati 9 , Jerzy Adamski 9, , Uwe Völker 2, , Matthias Nauck 1, & Nele Friedrich 1,
1Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany; 2DZHK (German Center for Cardiovascular Research), Partner site Greifswald, Greifswald, Germany; 3Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz Arndt-University Greifswald, Greifswald, Germany; 4Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Experimentelle Endokrinologie, Berlin, Germany; 5Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany; 6Medical Clinic I, University of Lübeck, Lübeck, Germany; 7Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; 8DZD (German Center for Diabetes Research), site Greifswald, Greifswald, Germany; 9Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany; 10Lehrstuhl fur Experimentelle Genetik, Technische Universität Munchen, München, Germany; 11DZD (German Center for Diabetes Research), München, Germany.
Background: Numerous animal models have shown impressive beneficial metabolic effects of the putative thyroid hormone (TH)-derivative 3,5-diiodothyronine (3,5-T2), including the prevention of insulin resistance or the reversal of hepatic steatosis, in the absence of thyrotoxic side effects. In contrast, the endogenous fate of 3,5-T2 in humans is still unclear. Comprehensive molecular profiling holds promise to gain deeper insights in metabolic alterations associated with serum 3,5-T2.
Methods: Among 856 participants of the Study of Health in Pomerania (SHIP-TREND) serum 3,5-T2 concentrations determined by chemiluminescence immunoassay were available. Metabolomics data were obtained using mass spectrometry and nuclear magnetic resonance spectroscopy, comprising 613 and 578 metabolites in plasma and urine, respectively. Linear regression analyses with either continuous or categorized 3,5-T2 concentrations were used to detect significant associations. Controlling for age, sex, waist circumference, thyrotropin and free thyroxine allowed assignment of thyroid function independent effects. Results were replicated in an experimental model of thyrotoxicosis comprising 16 male volunteers.
Results: Serum 3,5-T2 concentrations were not associated with thyroid function parameters nor altered during experimental thyrotoxicosis. The molecular fingerprint of 3,5-T2 comprised 15 and 73 significantly associated metabolites in plasma and urine, respectively. Metabolites related to coffee metabolism, including caffeine or paraxanthine, represented the most obvious molecular signature. This association was replicated under experimental thyrotoxic conditions.
Conclusion: The TH-independent molecular fingerprint of serum 3,5-T2 concentrations showed a clear and strong interference with coffee metabolism and points to the liver as potential target organ in the focus of local 3,5-T2 generation/action. Translating the beneficial effects seen in animal models, 3,5-T2 might provide a link between (high) coffee consumption and the decreased risk of metabolic diseases.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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