Urine Metabolomics by 1H-NMR Spectroscopy Indicates Associations between Serum 3,5-T2 Concentrations and Intermediary Metabolism in Euthyroid Humans

• Published in: European thyroid journal 2015-09, Vol.4 (Suppl 1), p.92-100
• Main Authors: Pietzner, Maik, Homuth, Georg, Budde, Kathrin, Lehmphul, Ina, Völker, Uwe, Völzke, Henry, Nauck, Matthias, Köhrle, Josef, Friedrich, Nele
• Format: Article
• Language: English
• Subjects: Clinical Thyroidology / Original Paper
• ISSN: 2235-0640; 2235-0802
• DOI: 10.1159/000381308

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 1 H-NMR spectroscopy. Multinomial logistic and multivariate linear regression models were used to detect associations between urine metabolites and serum 3,5-T 2 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.