3-Iodothyronamine: a novel hormone controlling the balance between glucose and lipid utilisation

Abstract

3-Iodothyronamine is considered as a derivate of thyroid hormone as a result of enzymatic deiodination and decarboxylation. The physiological role of thyronamine (T1AM) is not known. The aim of this study was to analyze the metabolic response to T1AM in the Djungarian hamster Phodopus sungorus. We measured the influence of T1AM (50 mg/kg) on metabolic rate (VO(2)), body temperature (T (b)) and respiratory quotient (RQ) in this species and in BL/6 mice. T1AM treated hamsters as well as the mice showed a rapid decrease in VO(2) and T (b), accompanied by a reduction of RQ from normal values of about approximately 0.9 to approximately 0.70 for several hours. This indicates that carbohydrate utilisation is blocked by the injection of T1AM and that metabolic pathways are rerouted from carbohydrate to lipid utilisation in response to T1AM. This assumption was further supported by the observation that the treatment of T1AM caused ketonuria and a significant loss of body fat. Our results indicate that T1AM has the potential to control the balance between glucose and lipid utilisation in vivo.

An online solid-phase extraction–liquid chromatography–tandem mass spectrometry method to study the presence of thyronamines in plasma and tissue and their putative conversion from 13C6-thyroxine

“…Besides the obvious species difference, our plasma samples were pooled samples taken between 5 and 120 min after injection, making direct comparison between their data and our data very difficult. In spite of the fact that endogenous levels of thyronamines published to date (Braulke et al 2008, Zucchi et al 2008) are above our LOD, to our surprise we did not detect any endogenous T 1 AM or T 0 AM. As can be observed in Fig.…”

“…As can be observed in panels C-E, a peak representing is above the highest calibration standard. Braulke et al (2008) showed that in Djungarian hamsters, serum T 1 AM levels were between 50 and 60 nmol/l 3 h after i.p. injection of 50 mg/kg T 1 AM.…”

“…It was, however, not until 2004 that Scanlan et al (2004) showed a major physiological role for thyronamines based upon elegant experiments in rodents. Systemic administration of 3-iodothyronamine (T 1 AM) and, to a lesser extent, of thyronamine (T 0 AM) induces profound metabolic and cardiac effects including bradycardia, hypothermia, and hyperglycemia (Scanlan et al 2004, Braulke et al 2008, Zucchi et al 2008, Dhillo et al 2009, Klieverik et al 2009). Both in vitro and in vivo studies have proposed potential receptors for thyronamines, i.e.…”

Design, Synthesis, and Evaluation of Thyronamine Analogues as Novel Potent Mouse Trace Amine Associated Receptor 1 (mTAAR1) Agonists

“…1, 13,14 While these effects occurred at micromolar concentration, metabolic and neurological effects were observed at lower dosages, which increased endogenous tissue concentration by about 1 order of magnitude. 15 T1AM favors fatty acid oxidation over carbohydrate oxidation, 16,17 and chronic treatment with exogenous T1AM in obese mice produced a significant reduction in body weight in the absence of changes in food consumption. 17 T1AM has also been reported to have neuromodulatory effects because icv administration in mice elicited pro-learning and antiamnestic effects.…”

A New Efficient Synthetic Method for 3-Iodothyronamine Involving Sonication and its Potent Hypothermic Efficacy

“…3,5 From the perspective of HS induction, 3-iodothyronamine (T 1 AM) has drawn a particular attention because it is an endogenous compound derived from deiodination and decarboxylation of thyroid hormone T 4 (thyroxine). The compound is shown to cause little side effect or damage on neural and other critical organs even for a long-term, repeated administration.…”