Journal
EUROPEAN THYROID JOURNAL
Volume 4, Issue -, Pages 92-100Publisher
KARGER
DOI: 10.1159/000381308
Keywords
3,5-Diiodothyronine; Trigonelline; Urine metabolome; NMR spectroscopy; Thyroid hormone
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Funding
- German Federal Ministry of Education and Research (BMBF) [01ZZ0403, 01ZZ0103, 01GI0883]
- Ministry for Education, Research and Cultural Affairs
- Ministry of Social Affairs of the Federal State of Mecklenburg-West Pomerania
- Federal Ministry of Education and Research
- Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania [03IS2061A]
- DFG SPP 1692 [WA 1328/5-1, KO 922/17-1, VO 955/12-1]
- DFG GRK [1208-2]
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Context: 3,5-Diiodo-L-thyronine (3,5-T-2) is a thyroid hormone metabolite which exhibited versatile effects in rodent models, including the prevention of insulin resistance or hepatic steatosis typically forced by a high-fat diet. With respect to euthyroid humans, we recently observed a putative link between serum 3,5-T-2 and glucose but not lipid metabolism. Objective: The aim of the present study was to widely screen the urine metabolome for associations with serum 3,5-T-2 concentrations in healthy individuals. Study Design and Methods: Urine metabolites of 715 euthyroid participants of the population-based Study of Health in Pomerania (SHIP-TREND) were analyzed by H-1-NMR spectroscopy. Multinomial logistic and multivariate linear regression models were used to detect associations between urine metabolites and serum 3,5-T2 concentrations. Results: Serum 3,5-T-2 concentrations were positively associated with urinary levels of trigonelline, pyroglutamate, acetone and hippurate. In detail, the odds for intermediate or suppressed serum 3,5-T-2 concentrations doubled owing to a 1-standard deviation (SD) decrease in urine trigonelline levels, or increased by 29-50% in relation to a 1-SD decrease in urine pyroglutamate, acetone and hippurate levels. Conclusion: Our findings in humans confirmed the metabolic effects of circulating 3,5-T-2 on glucose and lipid metabolism, oxidative stress and enhanced drug metabolism as postulated before based on interventional pharmacological studies in rodents. Of note, 3,5-T-2 exhibited a unique urinary metabolic profile distinct from previously published results for the classical thyroid hormones. (C) 2015 European Thyroid Association Published by S. Karger AG, Basel
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