title: Translating pharmacological findings from hypothyroid rodents to euthyroid humans: is there a functional role of endogenous 3,5-T2?
abstract: BACKGROUND
  During the last two decades, it has become obvious that 3,5-diiodothyronine (3,5-T2), a well-known endogenous metabolite of the thyroid hormones thyroxine (T4) or triiodothyronine (T3), not only represents a simple degradation intermediate of the former but also exhibits specific metabolic activities. Administration of 3,5-T2 to hypothyroid rodents rapidly stimulated their basal metabolic rate, prevented high-fat diet-induced obesity as well as steatosis, and increased oxidation of long-chain fatty acids.
  
  
  OBJECTIVE
  The aim of the present study was to analyze associations between circulating 3,5-T2 in human serum and different epidemiological parameters, including age, sex, or smoking, as well as measures of anthropometry, glucose, and lipid metabolism.
  
  
  METHODS
  3,5-T2 concentrations were measured by a recently developed immunoassay in sera of 761 euthyroid participants of the population-based Study of Health in Pomerania. Subsequently, analysis of variance and multivariate linear regression analysis were performed.
  
  
  RESULTS
  Serum 3,5-T2 concentrations exhibited a right-skewed distribution, resulting in a median serum concentration of 0.24 nM (1st quartile: 0.20 nM; 3rd quartile: 0.37 nM). Significant associations between 3,5-T2 and serum fasting glucose, thyrotropin (TSH), as well as leptin concentrations were detected (p<0.05). Interestingly, the association to leptin concentrations seemed to be mediated by TSH. Age, sex, smoking, and blood lipid profile parameters did not show significant associations with circulating 3,5-T2.
  
  
  CONCLUSIONS
  Our findings from a healthy euthyroid population may point toward a physiological link between circulating 3,5-T2 and glucose metabolism.
authors.affiliation: 1 Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald , Greifswald, Germany .
authors.forename: Maik
authors.initials: M
authors.lastname: Pietzner
authors.forename: Ina
authors.initials: I
authors.lastname: Lehmphul
authors.forename: Nele
authors.initials: N
authors.lastname: Friedrich
authors.forename: Claudia
authors.initials: C
authors.lastname: Schurmann
authors.forename: Till
authors.initials: T
authors.lastname: Ittermann
authors.forename: Marcus
authors.initials: M
authors.lastname: Dörr
authors.forename: Matthias
authors.initials: M
authors.lastname: Nauck
authors.forename: René
authors.initials: R
authors.lastname: Laqua
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.forename: Georg
authors.initials: G
authors.lastname: Brabant
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.forename: Henri
authors.initials: H
authors.lastname: Wallaschofski
mesh_terms: D000328:Adult; D000368:Aged; D004104:Diiodothyronines / Q000097:blood*; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood*; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D055815:Young Adult
chemical_list: D004104:Diiodothyronines; D020738:Leptin; D014284:Triiodothyronine; C030103:3,5-diiodothyronine; D013972:Thyrotropin; D013974:Thyroxine