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3-Iodothyronamine

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Thomas S Scanlan – One of the best experts on this subject based on the ideXlab platform.

  • N- and O-Acetylated 3-Iodothyronamines Have No Metabolic or Thermogenic Effects in Male Mice.
    European thyroid journal, 2019
    Co-Authors: Sogol Gachkar, Thomas S Scanlan, Heike Biebermann, Rebecca Oelkrug, Beate Herrmann, Qian Sun, Carolin S. Hoefig, Lutz Schomburg, Jens Mittag
    Abstract:

    Introduction Injection of 3-Iodothyronamine into experimental animals profoundly affects their metabolism and body temperature. As 3-Iodothyronamine is rapidly acetylated in vivo after injection, it was hypothesized that the metabolites N- or O-acetyl-3-Iodothyronamines could constitute the active hormones. Methods Adult male mice were injected once daily with one of the metabolites (5 mg/kg body weight intraperitoneally dissolved in 60% DMSO in PBS) or solvent. Metabolism was monitored by indirect calorimetry, body temperature by infrared thermography, and body composition by nuclear magnetic resonance analysis. Signaling activities in brown fat or liver were assessed by studying target gene transcription by qPCR including uncoupling protein 1 or deiodinase type 1 or 2, and Western blot. Results The markers of metabolism, body composition, or temperature tested were similar in the mice injected with solvent and those injected with one of the acetylated 3-Iodothyronamines. Conclusions In our experimental setup, N- and O-acetyl-3-Iodothyronamine do not constitute compounds contributing to the metabolic or temperature effects described for 3-Iodothyronamine. The acetylation of 3-Iodothyronamine observed in vivo may thus rather serve degradation and elimination purposes.

  • Proof of concept of the electrochemical sensing of 3-Iodothyronamine (T1AM) and Thyronamine (T0AM)
    ChemElectroChem, 2014
    Co-Authors: Luís Moreira Gonçalves, Thomas S Scanlan, Manuela M. Moreira, Carla F. Azevedo, Inês M. Valente, João Sousa, Richard G. Compton, José A. Rodrigues
    Abstract:

    Recent studies have shown that, besides the well-recognized T3 and T4 hormones, there are other relevant thyroid hormones circulating in the human body. In particular, this is the case for 3-Iodothyronamine (T1AM) and thyronamine (T0AM). One of the reasons for the lack of studies showing their precise importance is the absence of analytical methodologies available. Herein, for the first time, T1AM and T0AM are electrochemically characterized. T0AM was sensed by means of a glassy carbon electrode; furthermore, T1AM was sensed both with a graphitic surface (oxidatively) as well as with mercury (reductively). For both compounds, after oxidation, it was possible to observe the reversible redox reaction concerning the benzoquinone/hydroquinone couple, thus increasing the specificity of the electroanalysis. Therefore, this work provides the basis for an ‘at-point-of-use’ electrochemical strip test for T1AM and T0AM.

  • Biosynthesis of 3-Iodothyronamine (T1AM) is dependent on the sodium-iodide symporter and thyroperoxidase but does not involve extrathyroidal metabolism of T4.
    Endocrinology, 2012
    Co-Authors: Sarah A. Hackenmueller, Riccardo Zucchi, Maja Marchini, Alessandro Saba, Thomas S Scanlan
    Abstract:

    3-Iodothyronamine (T1AM) is an endogenous thyroid hormone derivative with unknown biosynthetic origins. Structural similarities have led to the hypothesis that T1AM is an extrathyroidal metabolite of T4. This study uses an isotope-labeled T4 [heavy-T4 (H-T4)] that can be distinguished from endogenous T4 by mass spectrometry, which allows metabolites to be identified based on the presence of this unique isotope signature. Endogenous T1AM levels depend upon thyroid status and decrease upon induction of hypothyroidism. However, in hypothyroid mice replaced with H-T4, the isotope-labeled H-T3 metabolite is detected, but no isotope-labeled T1AM is detected. These data suggest that T1AM is not an extrathyroidal metabolite of T4, yet is produced by a process that requires the same biosynthetic factors necessary for T4 synthesis.

Riccardo Zucchi – One of the best experts on this subject based on the ideXlab platform.

  • Exogenous 3-Iodothyronamine Rescues the Entorhinal Cortex from β-Amyloid Toxicity.
    Thyroid : official journal of the American Thyroid Association, 2019
    Co-Authors: Alice Accorroni, Sandra Ghelardoni, Alessandro Saba, Sabina Frascarelli, Martina Sabatini, Grazia Rutigliano, Marco Borsò, Elena Novelli, Lavinia Bandini, Riccardo Zucchi
    Abstract:

    Background: A novel form of thyroid hormone (TH) signaling is represented by 3-Iodothyronamine (T1AM), an endogenous TH derivative that interacts with specific molecular targets, including trace am…

  • Trace amine-associated receptor 1: a multimodal therapeutic target for neuropsychiatric diseases.
    Expert opinion on therapeutic targets, 2018
    Co-Authors: Michael D. Schwartz, Riccardo Zucchi, Stefano Espinoza, Juan J. Canales, I. Sukhanov, Raul R. Gainetdinov
    Abstract:

    ABSTRACTIntroduction: The trace amines, endogenous amines closely related to the biogenic amine neurotransmitters, have been known to exert physiological and neurological effects for decades. The recent identification of a trace amine-sensitive G protein-coupled receptor, trace amine-associated receptor 1 (TAAR1), and subsequent development of TAAR1-selective small-molecule ligands, has renewed research into the therapeutic possibilities of trace amine signaling.Areas covered: Recent efforts in elucidating the neuropharmacology of TAAR1, particularly in neuropsychiatric and neurodegenerative disease, addiction, and regulation of arousal state, will be discussed. Focused application of TAAR1 mutants, synthetic TAAR1 ligands, and endogenous biomolecules such as 3-Iodothyronamine (T1AM) has yielded a basic functional portrait for TAAR1, despite a complex biochemistry and pharmacology. The close functional relationship between TAAR1 and dopaminergic signaling is likely to underlie many of its CNS effects. How…

  • Lipolytic effects of endogenous 3-Iodothyronamine (T1AM) and synthetic analog SG-2 in vivo and in cultured adipocytes
    Endocrine Abstracts, 2017
    Co-Authors: Martina Sabatini, Riccardo Zucchi, Michael Rogowski, Fariba M. Assadi-porter, Ebru S. Selen Alpergin, Grazia Chiellini
    Abstract:

    3-Iodothyronamine (T1AM) is a hormone like molecule structurally similar to TH, that has been reported to modulate energy metabolism by favoring lipid over glucose catabolism. To better understand the role played by T1AM on the regulation of lipid metabolism, in the present study we administered spontaneously obese mice with T1AM at two different dosages (10 and 25 mg/kg per day) for 7 days and the effects on body weight (BW) and lipid profiles were examined. In addition a fluoro-labeled version of T1AM (FL-T1AM) was synthesized and utilized to assess T1AM intracellular localization in 3T3-L1 mouse adipocytes.\ud \ud Administration of 10 or 25 mg/kg per day T1AM showed a BW loss of 10% or 18% of initial BW by day 7 of treatment. T1AM treatment at both dosages produced a significant increase in total plasma triglycerides (P

Grazia Chiellini – One of the best experts on this subject based on the ideXlab platform.

  • 3-Iodothyronamine Affects Thermogenic Substrates’ Mobilization in Brown Adipocytes.
    Biology, 2020
    Co-Authors: Manuela Gencarelli, Grazia Chiellini, Annunziatina Laurino, Elisa Landucci, Daniela Buonvicino, Costanza Mazzantini, Laura Raimondi
    Abstract:

    We investigated the effect of 3-Iodothyronamine (T1AM) on thermogenic substrates in brown adipocytes (BAs). BAs isolated from the stromal fraction of rat brown adipose tissue were exposed to an adipogenic medium containing insulin in the absence (M) or in the presence of 20 nM T1AM (M+T1AM) for 6 days. At the end of the treatment, the expression of p-PKA/PKA, p-AKT/AKT, p-AMPK/AMPK, p-CREB/CREB, p-P38/P38, type 1 and 3 beta adrenergic receptors (β1–β3AR), GLUT4, type 2 deiodinase (DIO2), and uncoupling protein 1 (UCP-1) were evaluated. The effects of cell conditioning with T1AM on fatty acid mobilization (basal and adrenergic-mediated), glucose uptake (basal and insulin-mediated), and ATP cell content were also analyzed in both cell populations. When compared to cells not exposed, M+T1AM cells showed increased p-PKA/PKA, p-AKT/AKT, p-CREB/CREB, p-P38/P38, and p-AMPK/AMPK, downregulation of DIO2 and β1AR, and upregulation of glycosylated β3AR, GLUT4, and adiponectin. At basal conditions, glycerol release was higher for M+T1AM cells than M cells, without any significant differences in basal glucose uptake. Notably, in M+T1AM cells, adrenergic agonists failed to activate PKA and lipolysis and to increase ATP level, but the glucose uptake in response to insulin exposure was more pronounced than in M cells. In conclusion, our results suggest that BAs conditioning with T1AM promote a catabolic condition promising to fight obesity and insulin resistance.

  • Lipolytic effects of endogenous 3-Iodothyronamine (T1AM) and synthetic analog SG-2 in vivo and in cultured adipocytes
    Endocrine Abstracts, 2017
    Co-Authors: Martina Sabatini, Riccardo Zucchi, Michael Rogowski, Fariba M. Assadi-porter, Ebru S. Selen Alpergin, Grazia Chiellini
    Abstract:

    3-Iodothyronamine (T1AM) is a hormone like molecule structurally similar to TH, that has been reported to modulate energy metabolism by favoring lipid over glucose catabolism. To better understand the role played by T1AM on the regulation of lipid metabolism, in the present study we administered spontaneously obese mice with T1AM at two different dosages (10 and 25 mg/kg per day) for 7 days and the effects on body weight (BW) and lipid profiles were examined. In addition a fluoro-labeled version of T1AM (FL-T1AM) was synthesized and utilized to assess T1AM intracellular localization in 3T3-L1 mouse adipocytes.\ud \ud Administration of 10 or 25 mg/kg per day T1AM showed a BW loss of 10% or 18% of initial BW by day 7 of treatment. T1AM treatment at both dosages produced a significant increase in total plasma triglycerides (P

  • Thyronamines and Analogues – The Route from Rediscovery to Translational Research on Thyronergic Amines
    Molecular and cellular endocrinology, 2017
    Co-Authors: Grazia Chiellini, Martina Sabatini, Lorenza Bellusci, Riccardo Zucchi
    Abstract:

    Thyronamines are a novel class of endogenous signaling compounds, structurally related to thyroid hormones (THs). Specific thyronamines, particularly 3-Iodothyronamine (T1AM), stimulate with nanomolar affinity trace amine-associated receptor 1 (TAAR1), a G protein-coupled membrane receptor, and may also interact with other TAAR subtypes (particularly TAAR5), adrenergic receptors (particularly α2 receptors), amine transporters, and mitochondrial proteins. In addition to its structural similarities with THs, T1AM also contains the arylethylamine scaffold as in monoamine neurotransmitters, implicating an intriguing role for T1AM as both a neuromodulator and a hormone-like molecule constituting a part of thyroid hormone signaling. A large number of T1AM derivatives have already been synthesized. We discuss the different chemical strategies followed to obtain thyronamine analogues, their potency at TAAR1, and their structure-activity relationship. Preliminary characterization of the functional effects of these synthetic compounds is also provided.