title: Urine Metabolomics by (1)H-NMR Spectroscopy Indicates Associations between Serum 3,5-T2 Concentrations and Intermediary Metabolism in Euthyroid Humans.
abstract: BACKGROUND
  3,5-Diiodo-L-thyronine (3,5-T2) 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-T2 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-T2 concentrations in healthy individuals.
  
  
  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-T2 concentrations.
  
  
  RESULTS
  Serum 3,5-T2 concentrations were positively associated with urinary levels of trigonelline, pyroglutamate, acetone and hippurate. In detail, the odds for intermediate or suppressed serum 3,5-T2 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.
  
  
  CONCLUSIONS
  Our findings in humans confirmed the metabolic effects of circulating 3,5-T2 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-T2 exhibited a unique urinary metabolic profile distinct from previously published results for the classical thyroid hormones.
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, Greifswald, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Pietzner
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, Greifswald, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Budde
authors.affiliation: Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Lehmphul
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.affiliation: Institute for Community Medicine, University Medicine Greifswald, Ernst Moritz Arndt University, Greifswald, Germany.
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, Greifswald, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nauck
authors.affiliation: Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, Greifswald, Germany.
authors.forename: Nele
authors.initials: N
authors.lastname: Friedrich
keywords: 3,5-Diiodothyronine; NMR spectroscopy; Thyroid hormone; Trigonelline; Urine metabolome